Parkinson’s disease [PD] has been a great medical mystery for nearly two centuries. It was first identified by an English physician named James Parkinson who published a detailed description of it in an 1817 paper entitled “An Essay on the Shaking Palsy”  In 2015, PD affected around 2 million people globally resulting in 117,400 deaths [1]. The average life expectancy following diagnosis is between 7 and 15 years. PD is the second-most common neurodegenerative disorder in the United States. A lack of treatment options and an increasing elderly population will create a rising economic burden on patients. In 2010, it was estimated that approximately 630,000 people in the United States had been diagnosed with PD, with an economic burden exceeding $14.4 billion. By 2040, it is estimated that the prevalence of PD will double. More recently, a plethora of new pharmacological drugs have emerged as well as surgical options. The authors of this paper have had papers published associating mercury toxicity with Alzheimer’s disease [2], multiple sclerosis [3], mental illness [4], and amyotrophic lateral sclerosis [5]. Many of the symptoms associated with these maladies are also found in PD. The next step in our research was to explore the hypothesis that mercury may be associated with PD. If mercury is an etiological factor, where does it originate? The World Health Organization has stated that the largest source of mercury exposure to humans originates from the mercury in dental amalgams, which contain 50 percent mercury [6]. In the 19th century, dentists begin to use mercury amalgam in their dental practice. It is easy to work with and very pliable to fill dental caries [cavities]. Dentists proclaimed that mercury was safe, and that it did not escape from the filling. During the latter part of the 20th century the evidence proved otherwise. Studies found that mercury vapors were continuously being release from the amalgam in a non-ionized state. The mercury vapors were inhaled into the lungs, and 80 percent then entered the blood stream. The non-ionized mercury is able to cross the blood-brain barrier where it becomes ionized. Once ionized, the mercury becomes entrapped within the brain for up to several decades [7]. Controlled studies have shown once the dental amalgams are removed from a patient, their physical and mental health often improve [8]. Many PD symptoms are similar to mercury toxicity. This is the background for the study. The purpose of this paper is not to identify the source but determine if mercury could be causing PD.

To identify what physiologic, pathological, and mental symptoms occur in PD, a comprehensive PD book entitled The Encyclopedia of Parkinson’s Disease was used as the primary reference [9]. It was authored by Anthony Mosley, M.D. who specializes in PD. Each of the PD changes was identified and then cross referenced with mercury data bases and PubMed to identify scientific articles that could explain, and if so, how mercury might be causing these changes. Positive and negative reports were considered equally, and all data presented here helped explore the hypothesis. The study found that nearly all the changes that occur in PD could be explained by mercury toxicity. The following is a brief summary of the physiological, pathological, and mental changes occurring in PD, followed by evidence describing how mercury could cause these symptoms.

Hallmark Symptoms

Dopamine: Dopamine is a neurotransmitter that facilitates communication between central and peripheral neurons. Dopamine circulates as a fluid throughout the brain. It is essential for brain function that directs smooth coordinated movements. The substantia nigra, a small structure of the basal ganglia, produces most of brain dopamine. In PD, the cells in the substantia nigra reduce production of dopamine. The primary cause is the death of dopamine neurons in the brain [9].

Mercury: Mercury toxicity affects dopamine in a number of ways. Studies on minks found a significant negative correlation between total mercury and dopaminergic-2-receptors density [10]. Another study found dopamine levels were decreased in response to methylmercury exposure [11]. Epidemiological and vertebrate studies suggest that methyl mercury exposure may contribute to dopamine neuron vulnerability and propensity to develop PD [12]. Research has shown that mercury compounds alter dopaminergic synaptic function by disrupting calcium homeostasis [13].  Mercury exposure also has a significant negative effect on dopamine transporters in the striatum [14]. Other studies have shown methylmercury causes a reduction in skn-1 gene expression, which increases methylmercury-induced animal vulnerability and dopamine neuron degeneration [12].

Cardinal Symptoms: There are four cardinal symptoms associated with PD.

Resting Tremor: The tremor of PD is slow and steady. An imbalance of neurotransmitters in the basal ganglia permits erratic and chaotic communication among neurons. This effect overrides the thalamus [9].

Mercury: One of the hallmark symptoms of mercury toxicity is tremor. Gold miners use mercury to extract gold from ore. A common symptom of the gold miners was tremor [15]. A study of dentists who work with dental amalgam mercury found a positive association between mercury exposure and tremor.

Bradykinesia: Bradykinesia is defined as slowness of movement, which appears to be intentional. It is one of the earliest symptoms of PD. Bradykinesia accounts for much of the difficulty with balance [9].

Mercury: One study reports of a 55 year-old man who was exposed to mercury vapor during 33 years of working at a chemical plant that produced choline. At the age of 52, he developed bradykinesia [17]. Research on Wistar rats found methylmercury exposure for 5 days caused bradykinesia [18].

Rigidity: Rigidity is an increase in muscle tone that causes resistance to passive movement [9].

Mercury: One of the symptoms of gold miner workers exposed to mercury is muscle rigidity [19]. A 47 year-old dentist, exposed to mercury vapor, suffered from hemiparkinsonism whose symptoms included resting tremor and cogwheel rigidity [20]. He was treated with a mercury chelating agent d-penicillamine for a week to reduce the mercury. There was clinical improvement of Parkinsonism and an increase in urine mercury. A five-year followup found that his improved neurological status remained after treatment.

Postural Instability: This symptom presents itself as an inability to make adjustments in body position to maintain balance, equilibrium, and appropriate momentum during movement.  This symptom generates numerous gait disturbances [9].

Mercury: A study was done on Chinese miners who were exposed to mercury vapors. The workers suffered from tremors and postural sway caused by mercury exposure [21]. Another study was conducted on twelve Nubian goats who were given oral dosages of mercuric chloride. They developed abnormal posture [22]. One of the early symptoms of Minamata disease in Japan and a similar disease in Ontario, Canada due to eating fish contaminated with methyl mercury was postural tremor [23].

Muscle Symptoms

1. Balance: PD causes a progressive loss in the ability to maintain body balance, especially during movement [9].

Mercury: River dwellers in Brazil exposed to mercury often had a loss of balance when walking. Mercuric-chloride injected into the rat brain caused a decrease in balancing ability [24] [25].

2. Akinesia: This symptom is the absence of movement that typically manifests in PD. It manifests as difficulty in starting movement such as walking, and episodes become more frequent as PD develops [9].

Mercury: Studies were done on three marmosets who were given methylmercury for 14 days. All three showed slight akinesia before they were sacrificed [26].

3. Arm Swing: An arm swing that is asymmetrical is an early sign of PD. The degree to which the arm swing is reduced is one of the measures of PD [9].

Mercury: Mercury can cause asymmetrical symptoms [27].

4. Asymmetrical Symptoms: These symptoms occur primarily on the side of the body opposite the side of the affected brain. This is a typical symptom of PD [9].

Mercury: Infants with higher prenatal mercury exposure showed increased asymmetric reflexes among girls [P=0.04] [27].

5. Automatic Reflexes: These are defined as spontaneous actions the body takes without conscious awareness. In PD, automatic reflexes gradually diminish and eventually disappear as a result of disruption to basal ganglia [9].

Mercury: Nothing was found in the literature regarding mercury and automatic reflex. However, mercury is known to affect the basal ganglia. A study of rats given oral doses of inorganic mercury found that mercury ended up in the basal ganglia [28].

6. Autonomic Dysfunction: Changes to body functions regulated by the autonomic system are affected in PD. As the disease progresses, the neurotransmitter imbalance affects other organ systems in addition to the substantia nigra [9].

Mercury: A study on workers exposed to mercury vapor found they had losses in sympathetic autonomic activity when compared to a control [29].

7. Blepharospasm: Blepharospasm is a condition where there is involuntary contraction of eyelid muscles that can cause eyelid muscles to close. This can occur in PD [9].

Mercury: Nothing was found in the literature regarding mercury and blepharospasm. However, mercury can cause muscle spasm [30].

8. Blink Rate: The normal blink rate is ten times a minute. In PD, blinking can slow to a rate of 0 to 5 blinks a minute [9].

Mercury: Nothing in the literature was found regarding mercury and blink rate. However, mercury can affect eyelid muscles [30].

9. Bruxism: Bruxism is the involuntary grinding of the teeth together. The rigidity and spasms of PD can affect the muscles of the jaw causing the jaw to clamp shut [9].

Mercury: A study was done of nocturnal bruxism that was conducted on 88 female patients, which   concluded when the number of dental mercury amalgams was taken into account, there was a limited impact of bruxism associated with plasma mercury indicating that mechanical wear on amalgams from nocturnal bruxism may increase the mercury uptake [31].

10. Cog wheeling: Cog wheeling is a form of muscle rigidity characteristic of tremors in which muscles move with slight hesitation. Often it is an early sign of PD [9].

Mercury: A 47 year old female dentist, who had been exposed to mercury in her practice, suffered from hemi parkinsonism which had started 18 months earlier and was manifested by resting tremor and cogwheel rigidity.  She underwent chelation therapy for mercury and improved [20].

11. Communication Skills: People with PD often have difficulty in forming words and pushing sounds through vocal cords as a result of rigidity and bradykinesia [9].

Mercury: Autism is a neurological disorder that compromises communication skills. Mercury containing amalgams used to treat dental caries has been associated with higher rates of severe autism in children [32].

12. Coordination: The depletion of dopaminergic neurons in PD in the region of the brain that controls movement affects coordination in PD [9].

Mercury: Gold miners use mercury to extract gold from ore by adding the ligand mercury. Mercury levels in all exposed miners were elevated. One of the symptoms was coordination problems [15].

13. Physical Dexterity: In PD, the dexterity ability to perform tasks that require fine motor skills using fingers and hands gradually diminishes [9].

Mercury: A study was done on 129 adults in Brazil who were exposed to methyl mercury from fish consumption. Hair mercury levels were associated with poorer fine motor speed and dexterity. The study concluded that methylmercury was a risk factor in fine motor function and verbal memory, and may be a risk for neurocognitive function [33].

14. Hypokinetic Dysarthria: This is a common order in PD where there is speech difficulty as a result of bradykinesia involving muscles of the mouth and throat [9].

Mercury: A symptom of Minamata disease resulting from methylmercury in fish is dysarthria [23].

15. Dystonia: Dystonia is muscle rigidity or stiffness that prevents movement and forces the body into unusual positions resulting in painful muscle spasms. This may occur in PD and is thought to be cause by basal ganglia dysfunction [9].

Mercury: Nothing in the literature related mercury to dystonia. It is known that mercury can cause the basal ganglia to dysfunction [34].

16. Gait: In PD, gait disturbances may include short shuffling steps, limited arm swing, foot drag, and high stepping [9].

Mercury: Rat studies have shown mercury causes gait problems [35].

17. Gastric Motility: Due to the imbalance of dopamine and acetylcholine in PD, PD affects the action of smooth muscle tissue of the digestive tract [9].

Mercury: Studies on rabbits found the mercuric ion in mercury chloride induces contraction of vascular smooth muscle [36].

18. Hand Eye Coordiantion: People with PD have trouble with hand to eye coordination [9].

Mercury: Chronic exposure to mercury vapor in mine workers found that longer exposure to mercury correlated to poorer hand to eye coordination [37].

19. Hypomania: This is the clinical term for the composite of symptoms including reduced facial movement, slowed eye movement, slow blinking, and reduced facial expression. This occurs in PD when the disease affects the face [9].

Mercury: Nothing in the literature was found with the mercury/hypokinia relationship. Mercury is known to affect the muscles. One study found mice injected with mercury resulted in mercury accumulating in facial nerve nuclei [38].

20. Hypophonia: This condition is reduced voice volume. It occurs in PD when the vocal cord muscle are affected [9].

Mercury: Nothing in the literature directly connected mercury with hypophonia. However, mercury is known to affect most muscles [15].

21. Kinesia Paradoxia: This condition is a sudden and unexpected movement usually when walking that affect people with PD [9].

Mercury: Mercury can cause muscle spasms and tremors [15].

22. Micrographia: This is the clinical term for the tiny style of handwriting that is characteristic of subjects with PD [39].

Mercury: A study was done on 46 chloral-alkalai plant workers exposed to mercury vapors. Micrography was found in 58.7 percent of the workers [39].

23. Movement Disorders: This condition is considered one of the motor system disorders in PD [9].

Mercury: Workers exposed to mercury are known to have movement disorders [40].

24. Mobility: The neuromuscular symptoms such as bradykinesia and gait disturbance impair movement mobility [9].

Mercury: A study was done on subjects in Japan who developed Minamata disease after eating fish contaminated with methyl mercury. After several decades, their mobility had declined in all subjects [41].

25. Muscle Tone: In PD, muscle tone is increased due to a disruption of nerve signals from the basal ganglia because of a lack of dopamine [9].

Mercury: A study was done on 418 mother-neonate pairs analyzing mercury in the blood and cord. Cord blood mercury was significantly associated with passive and active muscle tone in neonates [42].

26. Myoclonus: Myoclunus is a sudden and brief contraction that gives the appearance of twitching or jerking in PD [9].

Mercury: A 23-year old woman injected herself with elemental mercury for two years. She developed disabling generalized myoclunus and ataxia [43].

27. Palladium: Palladium is a functional division of the basal ganglia, which is a cluster of neurons responsible for voluntary movement. In PD, the Globus palladium intern as malfunctions as dopinergic neurons continue to die [9].

Mercury: Nothing in the literature was found regarding mercury and the pallidium. In studies of rats who were given prolonged feeding of mercury it was found that mercury was deposited in the basal ganglia cytoplasm of large neurons [28].

28. Palsy: PD was once called shaking palsy. It is an antiquated term for temporary or permanent paralysis or inability to move [9].

Mercury: Prenatally mercury poisoned infants can develop severe cerebral palsy [44].    

29. Posture Stooping: A characteristic symptom of PD is a marked forward sloping of shoulders and limited upper body movement. It is one of the earliest symptoms of PD [9].

Mercury: Oral dosages of mercuric chloride were given to 12 nubian goats. The main symptoms were abnormal posture and recumbency [22].

30. Sexual Dysfunction: PD patients have difficulty in enjoying a satisfactory sexual relationship. Tremors and bradykinesia make movement and coordination difficult. Sixty percent of PD patients are affected [9].

Mercury: A study was done on gold miners who were exposed to mercury that found sexual dysfunction was one of the most serious symptoms [45].

31. Restless Leg Syndrome: Some PD patients report an involuntary twitching of the legs, usually when sitting or quietly at rest [9].

Mercury: One study found a significant relationship between restless leg syndrome and the number of mercury dental amalgams [46].

32. Spasm: Spasm is an intense involuntary contraction of a muscle or muscle group. The dystonia that develops in later stage PD is a severe spasm in which the muscle remained contracted for a long time [9].

Mercury: One of the symptoms of mercury toxicity is spasm [30].

33. Swallowing: The muscles involved in swallowing are sometimes affected in PD [9].

Mercury: Nothing in the literature was found regarding mercury and swallowing. It is known that mercury can affect most muscles [24].

34. Walking: The neuromuscular symptoms of PD such as bradykinesia interferes with walking [9].

Mercury: Mercury can cause bradykinesia that interferes with walking [24].

35. Eye Movements: The ability to control the movement of the eye becomes impaired in PD. Tremors and bradykinesia can affect the muscles that move the eye. Another eye symptom of PD may be difficulty in moving the eye such as reduction in blinking perhaps causing dry eyes and irritation. It does not appear PD affects vision itself [9].

Mercury: A study was done on 144 inhabitants in the riverside areas of Niigati, Japan. They had been intoxicated with organic mercury. Spontaneous and positional nystagmus [uncontrolled eye movements] were recorded in 94 of 144 subjects [47].

Physiology

1. Basal Ganglia: Basal ganglia is the collective term for the cluster of nerve cells, including substantia nigra, that control voluntary muscle movements. PD starts with the death of dopamine producing cells in the substantia nigra [9].

Mercury: Rats who were given a prolonged feeding of mercury chloride had mercury deposited in large neurons of the basal ganglia. It is known that mercury can cause neuron death [28].

2. 2. Blurred Vision: Many subjects with PD experience vision problems, which may be due to excess tears or inadequate tears. In PD bradykinesia can affect eye muscles [9].

Mercury: A Korean study on 23,376 subjects found an increase in odds of dry eyes that correlated with high mercury levels. Mercury is known to cause bradykinesia [48].

3. Brain: Cerebrum and Cerebellum: PD can affect the sensory function of the cerebrum early in the disease. Cognitive impairment typically occurs later on. The cerebellum regulates balance, posture, and coordination. All are affected in PD [9].

Mercury: Mercury concentrations were determined in autopsy samples of 46 Japanese subjects. Mercury accumulation was found in the cerebrum and cerebellum [49].

4. Catechol O Methyltransferase [COMT]: COMT is one of the two key enzymes that metabolizes dopamine in the brain [9].

Mercury: A study was done on human COMT levels and mercury. The data suggested that mercury exerts an enhancing effect on activity of COMT [50].

5. Constipation: Difficulty and delay in bowel movements is an early symptom of PD and becomes more severe as the disease progresses. The muscles of the intestinal tract are affected [9].

Mercury: One of the symptoms of mercury toxicity is constipation [51].

6. Incontinence: Often there is an inability to retain urine or feces in PD because of a lack of muscle control. Urine incontinence is more frequent [9].

Mercury: Nothing in the literature could be found regarding mercury toxicity and incontinence. One could hypothesize if mercury was involved it could be affecting the muscles that affect continence.

7. Pain: Pain is a common symptom in PD. Neuromuscular symptoms can create an awkward posture and limb position caused by bradykinesia that becomes uncomfortable [9].

Mercury: In India, all 32 patients who had experienced mercury toxicity from Siddha medicine suffered from intractable neuropathic pain. Mercury can cause bradykinesia [52].

8. Sleep Disturbances: PD patients often have problems in falling or staying sleep. Rigidity and bradykinesia make turning in bed difficulty [9].

Mercury: A study was conducted on villagers in Indonesia exposed to mercury from a nearby gold mine. Typical symptoms of mercury toxicity were found including sleep disturbances [53].

9. Substantia Nigra: The substanti nigra is found within the basal ganglia that produces nearly all the dopamine that the brain requires for neuron communication related to movement. This structure deteriorates in PD. Symptoms of PD occur when 80 percent of SNL dopamine neurons are destroyed [9].

Mercury: Accumulation of environmental toxins such as mercury are suggested as risk factors for developing late-onset PD. Occupational exposure to mercury has been found to increase the risk for PD. The substantia nigra is located in the basal ganglia and mercury can accumulate there after mercury exposure. It is known that mercury can cause neuron death and mutate genes [54].

10. Subthalamus: The subthalamus nucleus [STN] is a structure of the basal ganglia. The STN is a dense cluster of neurons in the center of the subthalamus. The dopamine depletion in PD allows the STN to become overactive in generating nerve signals to inhibit muscle activity. These signals flood the thalamus which in turn decreases excitation of the cerebral cortex that causes motor symptoms of bradykinesia and rigidity [9].

Mercury: Nothing in the literature was found regarding mercury and subthalamus. Mercury can cause tremors, bradykinesia, and rigidity.

11. Sweating: Excessive episodes of sweating are common in PD. It may be a consequence of damage to the autonomic nervous system as PD progresses [9].

Mercury: Sweating can be a symptom of mercury toxicity. A three - year old boy had been poisoned by mercury. One of his symptoms was sweating along with excessive salivation [55].

12. Thalamus: The thalamus is a structure in the brain that filters and organizes nerve signals between the cerebral cortex and other brain structures that control movement. A small area within the center of the thalamus becomes overactive resulting in tremors and rigidity [9].

Mercury:  Metallic mercury can induce tremors in rabbits. The concentration in the thalamus and cerebellum was significantly higher than in other structures. A positive causal relationship was found between tremor and mercury content of the CNS. Mercury can cause tremors,  bradykinesia and rigidity [56].

13. Urinary Frequency: PD patients often develop an urgency and frequent urination pattern. PD affects the function of smooth muscles found in the bladder and urinary tract [9].

Mercury: A total of 151 patients with Niigata Minamata disease caused by methyl mercury poisoning  from fish were studied. They developed lower urinary tract symptoms and over active bladder conditions that were severe and highly prevalent [57].

14. Urinary Retention: Incomplete emptying of the bladder is common in later stages of PD thought to be caused by the smooth muscle becoming impaired [9].

Mecury: Mercury toxicity can affect smooth muscles [36].

15. Weight Management: In later stage PD, low body weight often becomes a problem . Bradykinesia causes chewing and swallowing problems and PD patients eat less food. In earlier stage PD, patients have carbohydrate cravings that promote them to eat sweets [9].

Mercury: Mercury is associated with bradykinesia. Low doses of mercury exposure have been associated with obesity [58].

Hormones

1. Brain-derived Neurotrophic Factors [BDNF]: BDNF are natural substances, usually proteins that stimulate the growth of new nerve cells in the brain. When it is experimentally injected into the striatum of an animal with an experimental model of PD, it will cause new dopamine producing cells to start growing. Molecules of BDNF are too big to pass through the blood brain barrier [9].

Mercury: Rat studies found that methylmercury-induced cell death in the brain was accelerating BDNF [59].

2. Dopamine: In PD, cells in the substantia nigra reduce the body’s dopamine production. Symptoms begin when 80 percent of the substantia nigra cells have died. The primary cause of dopamine deficiency is the death of dopamine neurons in the brain [9].

Mercury: Epidemiological and vertebrate studies suggest that methylmercury exposure may contribute to dopamine vulnerability and the propensity to develop PD [12].

3. Estrogen: Health experts believe estrogen has a protective effect on a woman’s brain helping to stave off neurodegenerative disease including PD and Alzheimer’s disease [9].

Mercury: Estrogen is neurprotective. Rat studies found the toxicity of methylmercury in the hippocampus was enhanced by inhibiting synthesis of denovo synthesis of estradiol [60].

Biochemistry

1. Coenzyme Q-10: People with PD have lower levels of coenzyme Q-10, an antioxidant, compared to people without PD [9].

Mercury: Thirty one healthy James Bay fishermen were tested for oxidant and antioxidant effects for exposure to methylmercury during fishing season and off season. The antioxidant coenzyme Q-10 increased by 13 percent during fishing season suggesting it increases to help counteract mercury toxicity. This suggests that if mercury is involved in PD and levels of coenzyme Q-10 are reduced, the protection from free radicals would be reduced [61].

2. Complex 1: This is an enzyme within cell mitochondria that helps resist damage from free radicals. Studies have shown PD patients have low levels of complex 1 . Coenzyme Q-10 performs a similar function as complex 1 [9].

Mercury: Mercury causes the formation of free radicals. If PD patients have low levels of complex 1, they would be more susceptible to free radical damage to neurons [62].

3. Cytokines: Cytokines are chemicals produced in the body that cause inflammation. Brain cells of PD patients have elevated levels of cytokines [9].

Mercury: Mercury can cause inflammation and cytokine expression [63].

4. Excitotoxins: Excitotoxins are amino acid based substances that cause overstimulation of neurotransmitter receptors in the brain, resulting in neuro death. Some scientists believe that excitotoxins provide environmental impetus that sets in motion neurodegeneration that causes PD and Alzheimer’s disease [9].

Mercury: Powerful excitotoxins are linked to mercury toxicity [64].

5. Free Radicals: Free radicals cause damage that leave cells vulnerable to diseases such as PD and Alzheimer’s disease [9].

Mercury: Mercury toxicity significantly increases the levels of free radicals [62].

6. Gamma Aminobutyric Acid [GABA]: GABA is an amino acid that functions as an inhibitory transmitter in the brain. It reduces the sensitivity of muscle cells to nerve stimulation and decreases muscle movement. GABA is decreased in PD [9].

Mercury: Rat studies found that methylmercury chloride significantly inhibits GABA uptake into satellite cells in the earliest stages of poisoning. It also affects Schwann cells and ganglion cells [65].

7. Glutamate: Glutamate is an amino acid in the brain that functions as an excitatory neurotransmitter. As dopamine decreases with a progressive loss of neurons, glutamate binding increases which accelerates cell death and progression of PD [9].

Mercury: Studies on elemental mercury vapor found the blockade of the inactivation of synaptically released glutamate is a potential mechanism of central nervous system toxicity. Low concentrations of mercury can cause neurotoxicity by selectively inhibiting the uptake of synaptically released glutamate [66].

8. Glutathione: Glutathione is an antioxidant that clears the by products of dopamine metabolism from the brain. The action of glutathione becomes impaired in PD as well as Alzheimer’s disease allowing the by products to accumulate as free radicals [9].

Mercury: Studies have found an association between mercury and low levels of glutathione homestasis [67].

9. Mitochondrial Dysfunction: Mitochondrial dysfunction is emerging as a leading focus on the cause of PD. Mitochondrial electron transport chain is significantly less active in the neurons of PD patients impairing mitochondrial metabolism and causing dysfunction. PD patients tend to have increased metabolic rates thought to be caused by disruption of the mitochondrial transport chain affecting metabolism [9].

Mercury: Studies have found that mercury ions inhibit ATPase activity in mitochondria [68].

10. Monamine Oxidase [MAO]: MAO is an enzyme that metabolizes monamaine neurotransmitters such as dopamine. The MAO gene regulates mitochondria MAO production. Mutations in the MAO gene appear in some people with PD. Flaws in MAO regulation plays a role in depression. Half of PD patients experience depression [9].

Mercury: Mercury was found to affect MOA activity in different regions of the brain. Animal studies found exposure to methyl mercury corresponded to significant decreases in monamine oxidase activity in the brain [69].

11. Ubiquitin: This is a protein in the sequence of events called ubiquitin proteasome systems through which cells eliminate waste by-products. Malfunction allows molecules to accumulate in the cells. Scientists have found a number of mutations in the genes that regulate ubiquitin in PD and Alzheimer’s disease. This can result in accumulation of protein such as alpha-synuclein in PD. Ubiquitin has roles in repair of DNA and mitochondria metabolism and in the process of apoptosis [9].

Mercury: A study was done on hippocampal cells and how mercury affects them. The study found mitochondrial dysfunction and ubiquitin protesome dysfunction [70].

Mental Symptoms:

1. Agitation: Agitation often occurs in PD as the disease progresses and as a function of dementia and cognitive impairment [9].

Mercury: Mercury toxicity is associated with marked agitation and anxiety [71].

2. Bradyphrenia: This condition is defined as slowness in thinking and cognitive function. It appears in late stage PD. About half of PD patients experience problems of cognitive function [9].

Mercury: A study was done on 36 patients with chronic mercury intoxication. Changes were found in analytical and synthetic thinking, visual memory and cognitive impairment [72].

3. Cognitive Impairment: Cognitive impairment is a reduced ability to think, reason, analyze, or remember. The neurotransmitter imbalance between acetylcholine and dopamine interferes with cognition. It is common for PD patients to lose focus. Some people with PD experience severe and fluctuating cognitive impairment as the disease progresses [9].

Mercury: Patients with mercury intoxication experience cognitive impairment [2].

4. Confusion: Confusion is defined as a state of disorganized cognitive function. Transient confusion comes and goes and is often seen in later stage PD [9].

Mercury: Studies were done on 60 chlorine-alkali workers who were expose to inorganic mercury vapor. Symptoms included sleep disturbance, fatigue, and confusion [73].

5. Delirium: Delirium is defined as an alteration to levels of consciousness by marked mental confusion. In PD, delirium tends to be more common in the elderly and those with dementia [9].

Mercury: One of the symptoms of chronic occupation exposure to mercury is delirium [74].

6. Delusion: Delusion is defined as a false belief that something is real, when in fact it is untrue or imagined. Delusions are common in PD and tend to develop later in PD [9].

Mercury: It is hypothesized that delusions are caused by cholinergic disturbances in the dorsal striatum where nicotinic receptors are operative. Studies have found that mercuric chloride exerted a biphasic modulator effect on rat nicotinic acetylcholine receptors [75] [76].

7. Dementia: Dementia is a cognitive impairment that interferes with everyday activation and function including thinking and memory. It’s a programmed degeneration of brain function. The older a person is with PD, the more likely dementia will develop. There are several forms of dementia that accompany PD including Lewy body dementia and Alzheimer’s disease [9].

Mercury: Mercury has been linked to Alzheimer’s disease with evidence it may be an etiological factor [2]

8. Depression: About 40 percent of PD patients have depression. People with depression are more than three times likely to have PD than people who do not have depression [9].

Mercury: Studies have found that people with mercury dental fillings suffer significantly more from depression than subjects without mercury fillings. When amalgams are removed, depression is significantly reduced [2].

9. Dysphagia: This condition is a cognitive impairment causing difficulty with the spoken language that can occur in PD and Alzheimer’s disease [9].

Mercury: Nothing in the literature directly said that mercury causes dysphagia. Because dysphagia is a cognitive impairment, it is know that mercury affects cognition, a hallmark symptom [2].

10. Mental Dexterity: This is the ability to concentrate and quickly perform cognitive functions. It is diminished as PD progresses [9].

Mercury: Studies have shown that mercury toxicity diminishes cognitive functions [2].

11. Fatigue: Fatigue is defined as a persistent weariness and lack of energy. It is common in PD [9].

Mercury: Studies have shown that chronic mercury exposure, including dental amalgam mercury, is associated with fatigue, anxiety, and depression [77].

12. Hallucinations: A hallucination is a sensory perception of an event that is not really occurring. Visual hallucinations are common in PD [9].

Mercury: Studies have found that exposure to mercury can cause hallucinations [78].

13. Memory Impairment: Some degree of memory impairment is common in later stages of PD [9].

Mercury: One of the hallmark symptoms of mercury toxicity is memory impairment [2].

14. Mental Status: As PD progresses, the mental status shows a slow but steady decline [9].

Mercury: Studies have shown that a major effect of mercury toxicity is a cognition decline and memory loss [2].

15. Mood Swings: Mood swings are sudden extreme changes in emotions that are common in PD [9].

Mercury: Chronic low-levels of mercury exposure in dental assistants were found to increase symptoms of mood swings [79].

Genetic

1. Alpha-synuclein Gene: This is the first gene identified as having a role in familial predisposition to PD. It regulates how the body makes alpha-synuclein protein, which has a role and function of neurons in the brain. Only a handful of families have a mutation of this gene. It is believed that environmental factors may be the cause of a proportion of PD cases. Several PD genes are activated by xenobiotic exposure, and there has been a link between pesticides and PD. Epidemiological studies have shown an association between PD and exposure to metals such as mercury [9].

Mercury: Mercury is known to affect genes and DNA [80].

2. Autosomal Recessive Inheritance: This pattern of genetic transmission occurs when both parents carry mutated genes which is then transferred to the offspring. The Parkin gene mutation for PD is autosomic recessive [9].

Mercury: A study on Bloom’s syndrome, which is an autosomal recessive disorder, found mutations of the BLM gene [encoding BLM helicase] may be a cause of Bloom’s syndrome. Mercury inhibited the biological activity of BLM 642-1290 recombined helicase [81].

3. Chromosome: The extent to which gene mutation causes PD remains unknown. Mutations have been found on chromosomes [1]; [2-9], and [17]. The Parkin gene is found on chromosome [6]; [9].

Mercury: The incidence of chromosome aberration was studied on 22 men exposed to mercury vapor and organic mercury. None of the men were poisoned. The incidence of chromosome aberration was significantly higher [P = 0.001] in subjects exposed to mercury as compared with a control group of a similar mean age [82].

4. Gene: A number of gene mutations have been implicated in PD. Scientists believe that PD is caused by a combination of genetic predisposition and environmental triggers in PD. The extent to which genes influence PD is unknown [9].

Mercury: Mercury toxicity can cause gene mutations [80].

5. Parkin Gene: This is a gene located on chromosome 6 that is mutated in some people with PD [9].

Diet

1. Caffeine: Studies have shown that people who drink coffee have a reduced risk for developing PD. Some believe that caffeine blocks alpha adenosine receptor activation in the brain, a neurotransmitter that facilitates signals among neurons. Some scientists believe caffeine has a protection effect on various neurotransmitter receptors. Glutamate overstimulates certain receptors causing premature death of neurons. Caffeine is a glutamate antagonist [9].

Mercury: One study found that interferon y stimulation of mercury exposed dopaminergic neurons in neuro-inflammation diseases may diminish the neuro protective effects of coffee [83].

2. Calcium: Calcium along with potassium is needed for conduction of nerve signals. For the person with PD, assuring adequate calcium is especially important yet challenging. Many of the foods that are high in calcium are hard to swallow [9].

Mercury: Mercury upsets calcium homeostasis needed for nerve conduction [84].

Etiology

1. Chemical Toxins: A number of chemical toxins have been implicated in PD [9].
2. Pesticides and Herbicides: Studies have shown people who have had a higher than normal exposure to chemicals used for weeds and insects have a higher incidence of PD.
3. Polychlorinated Biphynels [PCB]: PCBs were common in thousands of products until they were banned in the United States in the 1970s. They contribute to accelerated aging and a decline in dopaminergic cells in the substantia nigra, and they increase the risk for developing PD. They have been linked to many health conditions.
4. Drugs: Some antipsychotic drugs used in treating schizophrenia can induce PD because they affect dopamine.
5. Mercury: Prolonged exposure to high levels of mercury has been associated with PD [9]. Mercury is a neurotoxin that accumulates in nerve cells.

Mercury is a persistent, bioaccummalative, neurotoxic metal that can accumulate in the brain. Since industrialization, mercury in the air and water has increased by three- to five-fold [85], and between 1977 and 2002 mercury increased four-to five- fold. Mercury in fish increases by about four percent every year. The half-life of mercury in the brain is from several years to several decades [7]. The World Health Organization rates mercury as one of the ten most dangerous chemicals to public health. A study on autopsied brains found that mercury concentrations in the occipital region of the brain increased with age [86]. Mercury exposure in humans is mainly derived from dental amalgams, fish consumption, air pollution, and mercury-based vaccines. The World Health Organization lists mercury from dental amalgams as being the greatest source. For decades, there has been a controversy regarding whether mercury exposure from these sources has clinical relevance. For fish consumption, there are confusing observations regarding healthy outcomes, because some kinds of fish are also big sources of selenium and omega-3 fatty acids which combat mercury toxicity. Additionally, the chemical form of mercury in fish already has reacted to molecules like cysteine and selenium. It may be much less toxic than the form which is used in toxicology studies or is produced in the gastrointestinal tract of humans by the methylation of inorganic mercury from dental amalgams [87] [88]. Surprisingly, mercury vapor seems to be more toxic in rats than unreacted methylmercury [89]. The question arises, which are the main sources of mercury in the brain? The monitoring of blood, urine, or other biological specimens in living organisms has not correlated appropriately with brain mercury content. Studies have found mercury can cause blood-brain barrier damage [90]. Once damaged, toxins can enter the brain with greater ease. The identical neural chemical lesions by mercury toxicity found in the rat brain were similar to or greater than those seen in Alzheimer’s brains. Methyl mercury has been shown to damage the central nervous system and is associated with vascular dysfunction, hemorrhages, and edema of the brain. Research has shown that mercury exposure can produce acute and chronic hypertension [91]. One study found that subjects with mercury dental amalgams had significantly higher blood pressure, systolic and diastolic, compared to an age- and sex- matched control group without dental analgams [92]. According to the World Health Organization [6], the greatest source of mercury originates from the dental amalgam, which contains 50 percent mercury. Mercury vapor is continuously released from the amalgam in the non-ionized state and then is inhaled. It then enters the lungs, and 80 percent of the mercury is taken up by the blood. The unionized mercury easily crosses the blood-brain barrier and becomes ionized. Once inside the brain, it becomes trapped, and has a half-life of up to several decades. If mercury is involved, it can cause pathological changes in the brain decades before PD is diagnosed [2]. Studies have already associated  mercury toxicity as being a possible etiological factor in PD. Evidence in this paper has been presented that explains how mercury can attribute to nearly all the physiological, pathological, and mental changes that occur in PD.

Evidence suggests that mercury could be an etiological factor in Parkinson’s disease. Mercury exposure has risen worldwide during the past century this is due to the fact that mercury is released in the biosphere through industrial activity and the burning of fossil fuels. It is being used for medicinal purposes and in dental fillings. The bottom line is that mercury is unable to degrade. Most of the U.S. population has been exposed to mercury from several sources, from prenatal to postnatal. There is strong evidence that mercury is associated with Alzheimer’s disease, multiple sclerosis, and mental health disorders. Could it also be a factor in Parkinson’s disease? The evidence says yes.

1. Kowal SL, Dall TM. Chakrabarti R, et al. The current and projected economic burden of Parkinson’s disease in the United States. Mov Disord, 2013; 28: 311-318.
2. Siblerud, R, Mutter J, Moore E, Naumann J, Walach H. A hypothesis and evidence that mercury may be an etiological factor in Alzheimer’s disease. International J of Environ Res and Public Health. 2019; 16: 24.
3. Siblerud R. Kienholz E. Evidence that mercury from silver dental fillings may be an etiological factor in multiple sclerosis. The Science of the Total Environment. 1994; 142: 191-205.
4. Siblerud R, Motl J, Kienholz E. Psychometric evidence that mercury from silver dental fillings may be an etiological factor in depression, excessive anger, and anxiety. Psychological Reports. 1994; 74: 67-80.
5. Mangelsdorf I, Walach H, Mutter J. Healing of amyotrophic lateral sclerosis: A case report. Complement Med Res. 2017; 24: 175-181.
6. Organization WHO, Health risks of heavy metals from long-range transboundary air pollution. WHO Regional Office for Europe. Copenhagen, Denmark. 2007.
7. Rooney JD. The retention of inorganic mercury in the brain. A systemic review of the evidence. Toxicol Pharm. 2014; 274:425-435.
8. Siblerud R. Health effects after amalgam removal. J of Orthomolecular Med. 1990; 5.
9. Mosley AD, Romaine DS. The Encyclopedia of Parkinson’s Disease, Amarath. New York 2004.
10. Basu N, Klenavie K, Ganberg M, Brien MO, Evans D, et al. Effects of mercury on neurochemical receptor characteristics in wild mink. Environ Toxicol Chem. 2005; 24: 1444-1450.
11. Martinez-Finley EJ, Caito S, Slaughter JC, Aschner M. The role of skn-1 in methylmercury induced latent dopaminergic neurodegeneration. Neuro chem Res. 2013; 38: 2650-2660.
12. Vanduyn N, Sellivari R, Wong G, Nass R. Skn-1/Nrf2 inhibits dopamine in a caenorhabdites elegans model of methylmercury toxicity. Toxicol Sci. 2010; 118: 613-624.
13. McKay SJ, Reynolds JN, Racz WJ. Effects of mercury compounds on the spontaneous and potassium-evoked release of (3H) dopamine from mouse striated slices. 1986.
14. Lin CY, Liou, SH, Hsiech CM, etal. Dose-response relationship between cumulative mercury exposure index and specific uptake ratio in the striatum Tc-99mTrodat Spect. 2011; 36: 689-693.
15. BoseO’Reilly S, Bernaudat L, Siebert U. Signs and symptoms of mercury exposed gold miners. Int J Occup Med Environ Health, 2017; 30: 249-269.
16. Anglen J, Gruninger E, Chou HN, et al. Occupational mercury exposure in multiple sclerosis and tremor among U.S. dentists. J Am Dent Assoc, 2015; 146: 659-668.
17. Miller K, Ochudlo S. Opala, G. Parkinsonism in chronic metallic mercury intoxication. 2003.
18. Oliveira AL, Pinheiro AM, Belem-Filho IJA, Fernandes LMP, Cartágenes SC, et al. Unraveling motor behavior hallmarks in intoxicated adolescents: methylmercury subtoxic-dose exposure and binge ethanol intake paradigm in rats. Environ Sci Pollut Res Int, 2018; 21937-21948.
19. Donoghue AM. Mercury toxicity due to the smelting of placer gold recovered by mercury amalgam. Occup Med Lond. 1998; 48: 413-415.
20. Finkelstein Y, Vardi J, Keston MM, Hod I. The enigma of parkinsonism in chronic borderline mercury intoxication resolved by challenge with penicillamine. Case Reports Neurotoxicology, 1996; 17: 291-95.
21. Iwata T, Sakamoto M, Feng X, Yoshida M, Jie Liu X, et al. Effects of mercury vapor exposure on neuromotor function in Chinese miners and smelters. Int Arch Occup Environ Health. 2007; 80:123-129.
22. Ahmed KE, Adam SE, Wahbi AA. Susceptibility of Nubian goats to mercury poisoning in the Sudan. Rev Elev Med Vet Pays Trup, 1991; 44: 123-129.
23. Jackson AC. Chronic neurological disease due to methylmercury poisoning. Review Can J. NeuroSci, 2018; 45:620-623.
24. Costa JMF, Lima AA, Rodrigues D, Khoury EDT, Souza GDS, et al. Emotional and motor symptoms in riverside dwellers exposed to mercury in the Amazon. Rev Bras Epidemiol, 2017; 20: 221-224.
25. Venable HL, Mills SH. Neurological and behavioral effects of intercranial administration of mercuric chloride on rats. J Toxicol Environ Health.1977; 3: 871-876.
26. Uezeno Y, Sasaki M, Eto K. Increased expression of aquaporin-4 with methylmercury exposure in the brain of the common marmoset. PMID: 22863855, 2012; 37: 749-763.
27. Xu X, Khoury JC, Sucharew H, Low level gestational exposure to mercury and maternal fish consumption. Neurotoxicol Teratol, 2016; 54: 61-67.
28. Brun A, Abdulla M, Samuelsson B. Uptake and localization of mercury in the brain of rats after prolonged oral feeding with mercuric chloride. Histochemistry. 1976; 47: 23-29.
29. Mitioni AL, Nagy BV, Moura ALA, etal. Neurotoxic impact of mercury on the central nervous system evaluated by neuropychological tests and on the autonomic nervous system evaluated by dynamic pupillometry. Neurotoxicology. 2017; 59: 263-269.
30. O’Carrol RE, Masterton G, Dougall N, Ebmeier KP, Goodwin GM. The neuropsychiatric sequella of mercury poisoning. The Mad Hatter’s disease revisited. Case Reports Br J Psychiatry. 1995; 167: 95-98.
31. Isacsson G, Barregard L, Seldon A, Bodin L. Impact of nocturnal bruxism on mercury uptake from dental amalgam. Eur J Oral Sci, 1997;105: 251-257.
32. Zeiden-Chulia F, Gurso UK, Konomen E, Gottfried C. A dental look at the autistic patient through orofacial pain. Review Acta Odontol Scand, 2011; 69: 193-200.
33. Lebel J, Mergler D, Branches F, Lucotte M, Amorim M, et al. Neurotoxic effects of low-level methylmercury contamination in the Amazonian basin, Environ Res. 1998; 79: 20-32.
34. Fawes RW, Ribaupierre Y, Guillemin MS, et al. Measurement of hand tremor by industrial exposure to metallic mercury. Br J Ind Med. 1983; 40: 204-208.
35. Day JJ, Reed MN, Newland MC. Neuromotor deficits and mercury concentrations in rats exposed to methylmercury and fish oil. Comparative study Neurotoxicol Teratol. 2005; 27: 629-691.
36. Solomon HS, Hollenberg NK. Catecholamine release: mechanism of mercury induced vascular smooth muscle contraction. Am J Physiol, 1975: 229: 8-12.
37. Roels K, Abdeladim S, Braun M. Detection of hand tremor in workers exposed to mercury vapor: A comparative study of three muscles. Environ Res. 1989; 49: 152-165.
38. Arvidson B. Accumulation of mercury in brainstem nucleus of mice after retrograde axonal transport. Acta Neurol Scand, 1990; 82: 234-247.
39. Pranjic N, Sinanovic O, Karamehic J, Jakuuboric R. Assessment of chronic neuropsychological effects of mercury vapor poisoning in chloral-alkalai plant workers. Bosn J Basic Med Sci, 2002; 2: 29-34.
40. Gillen Occupational neurotoxicity and movement disorders. A historical perspective. J Hist Neurosci, 1995; 4: 63-66.
41. Yorifuji T, Takaoka S, Grandjean P. Accelerated functional loss in congenital Minamata disease patient, Neurotoxicology and Teratology. 2018; 69: 49-53.
42. Wu J, Ying T, Shen Z, Wang H. Effect of low-level prenatal mercury exposure on neonate neuro-behavioral development in China, Pediatr Neurol, 2014; 51: 93-99.
43. Rayothaman M, Kulkarni G, Ashraf V, Pal DM, Chickabasavaiah Y, et al. Elemental mercury poisoning probably causes cortical myoclunus. Mov Disord, 2007; 22: 1964-1968.
44. Clarkson TW. Mercury: Major issues in environmental health. Review Environ Health Perspect, 1993; 100: 31-38.
45. Nayab G, Khan S, Khan A, Ahmad SS. Mercury health effects among the workers extracting gold from carpets and dusted clays through amalgamation and roasting processes. Environ Sci Pollut Res Int, 2015; 22: 17965-17974.
46. Szklarek M, Kostka T. The impact of the use of amalgam in dental treatment on the prevalence of restless leg syndrome in older people. Med Pr. 2019; 70: 9-16.
47. Mizukoshi K, Nagaba M, Ohno Y, etal. Neurotoxic studies upon intoxication by organic mercury compounds. J Otorbinolaryngal Relat Spec. 1975; 37: 74-87.
48. Jung SJ, Lee SH. Association between three heavy metals and dry eye disease in Korean adults: Results of the Korean national health and nutrition examination survey. Korean J Ophthalmol. 2019; 33: 26-35.
49. Matsuo N, Suzuki T, Akagi H. Mercury concentration in organs of contemporary Japanese. Arch Environ Health. 1989; 44: 298-303.
50. Boadi WY, Urbach J, Barnes ER. In vitro effect of mercury on ary 1 hydroxylase, quinone reductase, COMT, and glucose-6-phosphate dehydrogenase activities in term human placenta. Pharmacol Toxicol. 1991; 68: 317-21.
51. Zhou Z, Zhang X, Cui F, Liu R, Dong Z, Wang X, etal. Subacute motor neuron hyperexcitability with mercury poisoning: a case series and literature review. Review Eur Neurol. 2014; 72: 218-222.
52. Gnanshanmugan G, Balakrisham R, Somanasundaram SP. Mercury toxicity folowing unauthorized Siddha medicine intake - A mimicker of acquired neuromytonia. Indian Acad Neurol. 2018; 21: 49-56.
53. Reilly BOS, Schiul R, Nowak D, Siebert U, William JF, Owi FT, et al. A preliminary study on health effects in villages exposed to mercury in a small-scale artisanal gold mining area in Indonesia. Environ Res. 2016; 149: 274-281.
54. Ulversky VN, Li J, Fink AL. Metal triggered structural transformations, aggregation, and fibrillation of human alpha-synnucleins. A possible molecular NK between Parkinson’s disease and heavy metal exposure. J Biol Chem, 2001, 276: 44284-4496.
55. Tewell M, Spoto S, Wiese M. Mercury poisoning at a home day care center - Hillsborough County, Florida. Morb Mortal Wkly Rep. 2017; 66: 433-35.
56. Fukuda K. Metallic mercury induced tremor in rabbits and mercury content of the central nervous system. Br J Ind Med. 1971; 28: 308-311.
57. Hara N, Saito H, Takahashi K, Takeda M. Lower urinary symptoms in patients with Niigata Minamata disease: A case control study 50 years after methylmercury pollution. Int J Urol. 2013; 20: 610-15.
58. Wang G, Dibari J, Bind E, Steffens AM, Mukherjee J, Bartell TR, etal. In utero exposure to mercury and childhood overweight or obesity counteracting effect of maternal folate status. BMC Med. 2019; 19: 216.
59. Sakaue M, Mori N, Makita M, Makita M, Fujishima K, Hara S, et al. Acceleration of methylmercury-induced cell death of rat cerebellar neurons by brain-derived neurotrophic factor in vitro. Brain Res, 2009, 1273, 155-162.
60. Yamazaki T, Yamamoto M, Ishihara Y, Komatsu S, Munetsuna E, Onizaki, Ishida A, etal. Denovo synthesized estradiol protects against methylmercury - induced neurotoxicity in cultured rat hippocampal slices. PLoS One. 2013; 8.
61. Belanger MC, Mirault ME, Dewaily E, Michel P, Berthiaume L, Noel M, Seasonal mercury exposure and oxidant-antioxidant status of James Bay sport fishermen. Metabolism. 2008; 57: 630-636.
62. Glaser V, Nazari EM, Muller ME, Feksac L, Wannmacherd CMD, Rochae JBT, etal. Effects of inorganic selenium administration in methylmercury-induced neurotoxicity in mouse cerebral cortex. Int J Dev Neurosci, 2010, 28(7), 631-637.
63. Pollard KM, Cauui DM, Toomey CB, Hultm P, Dwight H. Mercury-induced inflammation and autoimmunity. Review Biochim Biophys Acta, 2019, 1863(12).
64. Blaylock RL. A possible mechanism in autism spectrum disorders, part 2: immunoexcitotoxicity. Altern Ther Health Med. 2009; 15.
65. Kumamoto N, Fukuhara N, Mayatake, T, Araki Kd, Takahashi Yd, Araki S. Experimental neuropathy induced by methylmercury compounds: autoradiographic study of GABA uptake by dorsal rood ganglia. Eur Neurol. 1986; 25: 269-277.
66. Brookes N. In vitro evidence for the role of glutamate in the CNS toxicity of mercury. Toxicology. 1992; 76: 245-256.
67. Robitaille S, Mailloux RJ, Chan HM. Methylmercury alters glutathione homeostasis by inhibiting glutaredoxin 1 and enhancing glutathione biosynthesis in cultured human astrocyte cells. Toxicol Lett. 2016; 256: 1-10.
68. Stara H, Drahota Z. Inhibition of mitochondria ATPase by Hg++ ions. Physiol Bohemoslov. 1978; 27: 193-98.
69. Bridges K, Venables B, Roberts A. Effects of dietary methylmercury on the dopaminergic system of adult fat head minnows and their offspring. Environ Toxicol Chem. 2017; 36: 1077-1084.
70. Karri V, Ramos D, Martinez JB. Odena A, Oliveira E, Coort SL, etal. Differential protein expression of hippocampal cells associated with heavy metals (Pb, As, and MeHg) neurotoxicity. Deepening into the molecular mechanism of neurodegenerative diseases. J Proteomics, 2018, 187, 106-125.
71. Siblerud RL. A comparison of mental health of multiple sclerosis patients with silver/mercury dental fillings and those with fillings removed. Psychological Reports. 1992; 70: 1139-1151.
72. Katoamanowa EW, Rukavishnikov VS, Lakhman OL, shevchenko OI, Denisova IO. Cognitive impairment in a toxic lesion of the brain. Neurol Dorkhiatr Im Skorsakova, 2015; 115: 11-15.
73. Piikivi L, Hanninen H. Subjective symptoms and psychological performance of chlorine-alkali workers, Scand. J Work Environ Health. 1989; 15: 69-74.
74. Faria M. Chronic occupational metallic mercurialism. Rev Saude Publica. 2003; 37: 116-27.
75. Mirzoian A, Leutje CW. Modulation of neuronal nicotinic acetylcholine receptors by mercury. J Pharmacol Exp Ther. 2002; 30: 560-567.
76. Caton M, Enrique LM, Ochoa M. The role of nicotinic cholinergic neural transmitters in delusional thinking. NPJ Schizopha. 2002; 6: 16.
77. Kern JK, Geier DA, Bjorklund G, King PG, Homme KG, Haley BE, et al.Evidence supporting a link between dental amalgams and chronic illness, fatigue, depression, anxiety, and suicide. Neuro Endocrinal Lett. 2014; 35: 537-552.
78. Azevedo BF, Furieri LB, Pecanha FM, Wiggers GA, Vassallo PF,  Simoes MR, J etal. Toxic effects of mercury on the cardiovascular and central nervous systems. J Biomed Biotechnol. 2012; 949048 doi.
79. Heyer NJ, Echeverria D, Bittner AC, Farin FM, Garabedian CC, Woods JS . Chronic low-level mercury exposure, BDNF polymorphism, and associations with self-reported symptoms and mood. Toxicol Sci. 2004; 81: 354-63.
80. Ariza ME, Williams MV. Lead and mercury mutagenesis: types of mutation dependent upon metal concentration. J Biochem Mol Toxicol. 1999; 13: 107-112.
81. Chen X, Luo H, Duan L, Xu Q, Zhang Y, Xu H. Effects of mercury on the structure and activity of BLM 642-1290 recombinant helicase. Biomed Environ Sci, 2011, 24(1), 47-55.
82. Popescu HI, Negru L, Lancrajan I. Chromosome aberrations induced by occupational exposure to mercury. Arch Environ Health. 1979; 34: 461-463.
83. Engin AB, Engin ED, Golokhvast K, Demetrios KGA. Spandidos Aristides M. Tsatsakis etal. Glutamate mediated effects of caffeine and interferon y on mercury-induced toxicity. Int J Mol Med, 2017, 39(5), 1215-1223.
84. Suzuki N, Yamamoto M, Watanabe K, Kambegawa A, Hattori A . Both mercury and cadmium influence calcium homeostasis resulting from the suppression of scale bone cells: the scale is a good model for the evaluation of heavy metals in bone metabolism. J Bone Miner Metab. 2004; 22: 439-446.
85. Drevnick PF, Lamborg CH, Horyan MJ. Increase in mercury in Pacific yellow fin tuna. Environ Toxicol Chem. 2015; 34: 931-34.
86. Weiner JA, Nylander M. The relationship between mercury concentrations in human organs and predictor variables. Sci Tot Environ. 1993; 138: 101-115.
87. Haris HH, Pickering JJ, George GN. The chemical form of mercury in fish. Sci. 2003; 301: 1203.
88. Heintze U, Edwardsson S, Derand F, Birkhed D. Methylation of mercury from amalgam and mercury chloride by oral streptococci in vitro. Scand J Dent Res. 1983; 91: 150-152.
89. Fredriksson A, Dencker I, Archer T. Prenatal exposure to metallic mercury vapor and methyl mercury provides interactive behavioral changes in rats. Neurotoxicol Teratol. 1996; 18: 129-134.
90. Takahashi T, Fujimura M, Koyama M. Methylmercury causes blood-brain barrier damage in rats via upregulation of vascular growth factor expression. PLoS One. 2017; 12: e170623.
91. Martins ADCJ, Carneiro MFH, Grotto D, Adeyemi JA, Barbosa FJ etal. Arsenic, cadmium, mercury induced hypertension mechanisms and epidemiological findings. J Toxicol Environ B Crit Rev, 2018, 21, 61-82.
92. Siblerud RL. The relationship between mercury from dental amalgams and the cardiovascular system, Sci Total Environ. 1990; 99: 23-35.