Effects Of Manganese Exposure Research Articles

GLAST Activity is Modified by Acute Manganese Exposure in Bergmann Glial Cells.

Glutamate is the major excitatory amino acid neurotransmitter in the vertebrate brain. It exerts its actions through the activation of specific plasma membrane receptors expressed in neurons and glial cells. Overactivation of glutamate receptors results in neuronal death, known as excitotoxicity. A family of sodium-dependent glutamate transporters enriched in glial cells are responsible of the vast majority of the removal of this amino acid form the synaptic cleft. Therefore, a precise and exquisite regulation of these proteins is required not only for a proper glutamatergic transmission but also for the prevention of an excitotoxic insult. Manganese is a trace element essential as a cofactor for several enzymatic systems, although in high concentrations is involved in the disruption of brain glutamate homeostasis. The molecular mechanisms associated to manganese neurotoxicity have been focused on mitochondrial function, although energy depletion severely compromises the glutamate uptake process. In this context, in this contribution we analyze the effect of manganese exposure in glial glutamate transporters function. To this end, we used the well-established model of chick cerebellar Bergmann glia cultures. A time and dose dependent modulation of [3H]-D-aspartate uptake was found. An increase in the transporter catalytic efficiency, most probably linked to a discrete increase in the affinity of the transporter was detected upon manganese exposure. Interestingly, glucose uptake was reduced by this metal. These results favor the notion of a direct effect of manganese on glial cells, this in turn alters their coupling with neurons and might lead to changes in glutamatergic transmission.

The effect of manganese exposure on GnRH secretion via Nrf2/mGluR5/COX-2/PGE2/signaling pathway.

There are limited studies focused on the precise mechanism of gonadotropin-releasing hormone (GnRH) secretion dysfunction after overexposure to manganese (Mn). The objective of the present study was to explore the mechanism of Mn disruption of GnRH synthesis via nuclear factor erythroid-2-related factor-2 (Nrf2)/metabotropic glutamate receptor-5 (mGluR5)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) signaling pathway in vitro and in vivo. Primary astrocytes were cultured and treated with different doses of Mn, tert-butylhydroquinonet (tBHQ; Nrf2 agonists), 3-[(2-methyl-4-thaizolyl) ethynyl] pyridine (MTEP; mGluR5 inhibitor), and celecoxib (COX-2 inhibitor) to measure the levels of COX-2, mGluR5, Nrf2, and Nrf2 target genes. Mice were randomly divided into 11 groups, of which included the control group, 12.5-, 25-, and 50-mg/kg MnCl2 group, dimethyl sulfoxide (DMSO) group, tBHQ control group, tBHQ pretreatment group, MTEP control group, MTEP pretreatment group, celecoxib control group, and celecoxib pretreatment group. The injection was administered every day for 2 weeks. Then, levels of GnRH, PGE2, COX-2, mGluR5, Nrf2, Nrf2 target genes, and morphological changes in the hypothalamus of mice were measured. Mn reduced protein levels of Nrf2 and mRNA expression of Nrf2 target genes and increased mGluR5, COX-2, PGE2, and GnRH levels. Meanwhile, injury-related histomorphology changes in the hypothalamus of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GnRH secretion through Nrf2/mGluR5/COX-2/PGE2 signaling pathway.

Mediating and Interacting Effects of Birth Outcomes on the Relationship between Prenatal Manganese Exposure and Cognitive Outcome among 2-3 years-old Bangladeshi Children

Background/Aim: We investigated the mediating and interacting influence of physical measurements at birth on the relationship between prenatal exposure to manganese and cognitive status among 2-3 years-old Bangladeshi children. Methods: Pregnant mothers were enrolled in a prospective birth cohort in rural Bangladesh between 2008-2011 and children followed longitudinally. Manganese was measured in umbilical cord blood metal by ICP-MS. Anthropometric measurements (weight, length, head circumference) were assessed at delivery. Cognitive status of the children was assessed by translated and culturally appropriate version of the Bayley Scales of Infant and Toddler Development Third Edition at age 20-40 months. We assessed the effect of cord blood manganese on neurodevelopment considering whether physical measures at birth mediated the association with cognitive score or whether these measures modified the association between cord blood manganese and cognitive score. Recently developed statistical approaches allow for estimating mediation and effect modification effects simultaneously. Results: 764 mother-child pairs were included. Higher cord blood manganese concentration was associated with lower cognitive score [β=-0.31, standard error (SE)=0.12, p=0.008]. Among the birth measures, mediating and modifying effects of birth length were identified. We found a significant mediation effect through birth length (β =-0.08, SE=0.03). We found evidence of interaction between manganese and birth length (β =0.11, SE=0.03) and of mediated interaction (both mediation and interaction)(β =-0.04, SE=0.01)(all p≤0.01). The overall proportion mediated by birth length was 38.2% and the proportion attributed to interaction was 21.7%. Conclusions: Our findings confirm that birth length significantly contributes to the overall effect of manganese exposure on child’s cognitive score. This suggests that manganese may have effects on global nutritional status that contributes to neurotoxicity, as opposed to effects that are specific to brain development. In addition, our analysis suggests that birth length (a marker of growth stunting) also partly modifies the effect of manganese on neurodevelopment.

The effect of manganese exposure in Atp13a2-deficient mice

Loss of function mutations in the P5-ATPase ATP13A2 are associated with Kufor-Rakeb Syndrome and Neuronal Ceroid Lipofuscinosis. While the function of ATP13A2 is unclear, in vitro studies suggest it is a lysosomal protein that interacts with the metals manganese (Mn) and zinc and the presynaptic protein alpha-synuclein. Loss of ATP13A2 function in mice causes sensorimotor deficits, enhanced autofluorescent storage material, and accumulation of alpha-synuclein. The present study sought to determine the effect of Mn administration on these same outcomes in ATP13A2-deficient mice. Wildtype and ATP13A2-deficient mice received saline or Mn at 5–9 or 12–19 months for 45days. Sensorimotor function was assessed starting at day 30. Autofluorescence was quantified in multiple brain regions and alpha-synuclein protein levels were determined in the ventral midbrain. Brain Mn, iron, zinc, and copper concentrations were measured in 5–9 month old mice. The results show Mn enhanced sensorimotor function, increased autofluorescence in the substantia nigra, and increased insoluble alpha-synuclein in the ventral midbrain in older ATP13A2-deficient mice. In addition, the Mn regimen used increased Mn concentration in the brain and levels were higher in Mn-treated mutants than controls. These results indicate loss of ATP13A2 function leads to increased sensitivity to Mn in vivo.

Effects of Manganese Exposure on Blood Iron Indices in Miners of Iran Manganese Mines Co. (Qom)

Background: In present study, chronic exposure to manganese (Mn) and its effect on blood iron (Fe) indices in miners of Iran manganese mines-Qom have been investigated. Methods: In this cross-sectional study, fifty six miners and 5 control persons were studied cross sectionally. Prior to beginning of daily work, miners filed questionnaire and then their blood, urine and saliva samples were collected. Mn concentrations in samples were analyzed by atomic absorption spectroscopy (AAS). CBC analysis was performed by auto-analyzer system and blood Fe, transferrin (Tf), ferritin (Fr), total iron binding capacity (TIBC) and hemoglobin (Hb) were determined by respected commercial kits. Results processed by using software SPSS 16. Results: Between measured indices, only blood Mn, Fe and TIBC had significant difference in miners and controls (P < 0.05). The results showed that although Mn and Fe level increased in serum of miners but did not cause anemia. Result even the maximum manganese of blood, 1580 μg/L has not had undesired effects on miners iron homeostasis. Conclusions: Therefore Mn mining and Mn accumulation in blood did not increase the risk of impaired iron homeostasis. This may be due to co-exposure to Fe (in braunite (Mn mineral)) and/or compensatory mechanisms that don’t allow to wide range changes in blood parameters. Also personal discrepancy, social status, life style and place may influence the results of present study.

Effects of manganese exposure on visuoperception and visual memory in schoolchildren

BackgroundManganese (Mn) is an essential metal involved in multiple physiological functions. Environmental exposure to airborne Mn is associated with neurocognitive deficits in humans. Children, whose nervous system is in development, are particularly susceptible to Mn neurotoxicity. ObjectiveThe objective of this study was to assess the association between Mn environmental exposure, and effects on visuoperception and visual memory in schoolchildren. MethodsWe assessed schoolchildren between 7 and 11 years old, with similar socioeconomic status, from the mining district of Molango (n=148) and Agua Blanca (n=119, non-mining area) in Hidalgo state, Mexico. The Rey-Osterrieth Complex Figure (ROCF) test was used to assess visuoperception and short-term visual memory. Hair manganese (MnH) concentrations were determined. Linear regression models were constructed to estimate the associations between MnH and ROCF scores, adjusted for potential confounders. ResultsThe geometric mean MnH was nine times higher in schoolchildren from the Mn mining area (5.25μg/g) than in schoolchildren from the non-mining area (0.55μg/g). For the ROCF Copy trial, MnH was significantly associated with an increase in distortion errors (tangency, closure), angle errors, overtracing (partial overtracing). In the Immediate Recall trial, MnH was significantly associated with increased overtracing (partial overtracing) and omissions, and negatively associated with the number of perceptual drawn units, total score and percentage immediate recall. ConclusionsMnH is associated with alterations in visuoperception and short-term visual memory in schoolchildren exposed to airborne Mn.

Effects of manganese exposure on visuoperception and visual memory in schoolchildren.

Objectives: Manganese (Mn) is an essential element involved in multiple physiological functions. Environmental exposure to airborne manganese is associated with neurocognitive deficits. Children, w...

Effects of manganese exposure on crayfish motility.

Manganese (Mn) is a metal ion that is essential for healthy brain functioning at low levels (Quintanar, 2008). However, excessive exposure to Mn can lead to manganism — a neurodegenerative disease that manifests in Parkinsonian symptoms. High levels of Mn are found in hazardous occupational environments, especially in the mining and welding industries. In addition to the Parkinsonian symptoms associated with exposure to high levels of Mn, low to moderate Mn exposure has been linked with subtle impairments, such as hyperactivity and decreased cognitive abilities (Neal and Zheng, 2015). These low to moderate exposures can occur due to unregulated Mn levels in public tap water, which is especially prone to infiltration of neurotoxic chemicals in regions with high levels of mining activity (Quintanar, 2008). It was hypothesized that low to moderate Mn exposure in crayfish would be associated with altered motility in a T-maze. Crayfish exposed to varying levels of Mn were tested in a two-arm T-maze with a lighted arm and a dark arm. Movements and behavior were analyzed with video tracking software EthoVision XT 11. Behaviors of interest, including place preference to maze zones, choice behaviors, and general activity levels were recorded. We expect that Mn exposure will be associated with significant deficits in crayfish motility, which can be inferred to affect decision-making and risk-taking behaviors.

Effects of Manganese Exposure on Olfactory Functions in Teenagers: A Pilot Study.

Long-term exposure to environmental manganese (Mn) affects not only attention and neuromotor functions but also olfactory functions of a pre-adolescent local population who have spent their whole life span in contaminated areas. In order to investigate the effect of such exposure at the level of the central nervous system we set up a pilot fMRI experiment pointing at differences of brain activities between a non-exposed population (nine subjects) and an exposed one (three subjects). We also measured the volume of the olfactory bulb as well as the identification of standard olfactory stimuli. Our results suggest that young subjects exposed to Mn exhibit a reduction of BOLD signal, subjective odor sensitivity and olfactory bulb volume. Moreover a region of interest SPM analysis showed a specifically reduced response of the limbic system in relation to Mn exposure, suggesting an alteration of the brain network dealing with emotional responses.

An analysis of manganese level and results of occupational health inspection among workers in a workplace

To understand the toxic effects of manganese exposure on health by measurement of manganese concentration and occupational health inspection among workers in an enterprise exposed to manganese, and to provide a basis for occupational disease control. The air concentrations of manganese in 12 workplaces where workers often stayed were measured by typical sampling; occupational health inspection was performed among a total of 538 workers in the enterprise by cluster sampling. The average concentrations of manganese in the workplace from 2011 to 2013 were 0.179 mg/m(3), 0.122 mg/m(3), and 0.082 5 mg/m(3), respectively, indicating a significant decrease in manganese level within the three years by rank-sum test (P < 0.05). The results of health inspection showed that 165 (30.7%) out of 538 workers had abnormal indices, and the incidence of autonomic nervous system abnormalities reached 32.7% (176/538). There was no correlation between manganese concentration in the workplace and the incidence of abnormal indices in health inspection, while the manganese concentration in the workplace was positively correlated with the incidence of autonomic nervous system symptoms (r = 0.718, P < 0.05). The manganese concentration in the workplace is positively correlated with the incidence of autonomic nervous system symptoms. Early exposure to a low level of manganese can induce functional changes and potential damages in the nervous system.

Neurobehavioral and -physiological effects of manganese exposure in welders

Neurobehavioral and -physiological effects of manganese exposure in welders

Expression and Transport of α-Synuclein at the Blood-Cerebrospinal Fluid Barrier and Effects of Manganese Exposure.

The choroid plexus maintains the homeostasis of critical molecules in the brain by regulating their transport between the blood and cerebrospinal fluid (CSF). The current study was designed to investigate the potential role of the blood-CSF barrier (BCSFB) in α-synuclein (a-Syn) transport in the brain as affected by exposure to manganese (Mn), the toxic metal implicated in Parkinsonian disorders. Immunohistochemistry was used to identify intracellular a-Syn expression at the BCSFB. Quantitative real-time PCR was used to quantify the change in a-Syn mRNA expression following Mn treatments at the BCSFB in vitro. ELISA was used to quantify a-Syn levels following in vivo and in vitro treatments of Mn, copper (Cu), and/or external a-Syn. Thioflavin-T assay was used to investigate a-Syn aggregation after incubating with Mn and/or Cu in vitro. A two-chamber Transwell system was used to study a-Syn transport by BCSFB monolayer. Data revealed the expression of endogenous a-Syn in rat choroid plexus tissue and immortalized choroidal epithelial Z310 cells. The cultured primary choroidal epithelia from rats showed the ability to take up a-Syn from extracellular medium and transport a-Syn across the cellular monolayer from the donor to receiver chamber. Exposure of cells with Mn induced intracellular a-Syn accumulation without causing any significant changes in a-Syn mRNA expression. A significant increase in a-Syn aggregation in a cell-free system was observed with the presence of Mn. Moreover, Mn exposure resulted in a significant uptake of a-Syn by primary cells. These data indicate that the BCSFB expresses a-Syn endogenously and is capable of transporting a-Syn across the BCSFB monolayer; Mn exposure apparently increases a-Syn accumulation in the BCSFB by facilitating its uptake and intracellular aggregation.

Regulation of Copper Transport Crossing Brain Barrier Systems by Cu-ATPases: Effect of Manganese Exposure

Regulation of cellular copper (Cu) homeostasis involves Cu-transporting ATPases (Cu-ATPases), i.e., ATP7A and ATP7B. The question as to how these Cu-ATPases in brain barrier systems transport Cu, i.e., toward brain parenchyma, cerebrospinal fluid (CSF), or blood, remained unanswered. This study was designed to characterize roles of Cu-ATPases in regulating Cu transport at the blood-brain barrier (BBB) and blood-CSF barrier (BCB) and to investigate how exposure to toxic manganese (Mn) altered the function of Cu-ATPases, thereby contributing to the etiology of Mn-induced parkinsonian disorder. Studies by quantitative real-time RT-PCR (qPCR), Western blot, and immunocytochemistry revealed that both Cu-ATPases expressed abundantly in BBB and BCB. Transport kinetic studies by in situ brain infusion and ventriculo-cisternal (VC) perfusion in Sprague Dawley rat suggested that the BBB was a major site for Cu entry into brain, whereas the BCB was a predominant route for Cu efflux from the CSF to blood. Confocal evidence showed that the presence of excess Cu or Mn in the choroid plexus cells led to ATP7A relocating toward the apical microvilli facing the CSF, but ATP7B toward the basolateral membrane facing blood. Mn exposure inhibited the production of both Cu-ATPases. Collectively, these data suggest that Cu is transported by the BBB from the blood to brain, which is mediated by ATP7A in brain capillary. By diffusion, Cu ions move from the interstitial fluid into the CSF, where they are taken up by the BCB. Within the choroidal epithelial cells, Cu ions are transported by ATP7B back to the blood. Mn exposure alters these processes, leading to Cu dyshomeostasis-associated neuronal injury.

Prolactin levels in manganese-exposed male welders

Early studies on manganese (Mn) exposure have demonstrated that this transition metal affects dopamine neurotransmission. Dopamine serves as a tonic inhibitor of prolactin release in the anterior hypophysis. Our aim was to determine the relation between serum prolactin levels and manganese-exposure. Whole blood was collected from 95 non-exposed control subjects and 179 manganese-exposed male welders. Whole blood manganese was analyzed by Inductively Coupled Plasma--Mass Spectrometer on Agilent 7700 (Agilent Technologies, USA). Serum prolactin levels (PRL), aspartate transaminase (AST), alanine transaminase (ALT), urea, creatinine, soduim (Na), potassium (K) were analyzed by immunological and spectrophotometric methods on Roche E170 Modular System (Roche Diagnostics, Mannheim, Germany). The mean ages for control and manganese-exposed group were 40.5 ± 7.8 and 39.5 ± 8.7, respectively (p = 0.258). The mean working period (years) for control and manganese-exposed group were 17.4 ± 9.8 and 18.2 ± 7.7 years, respectively (p = 0.581). Serum AST and potassium levels were significantly higher in control group than manganese-exposed group (p = 0.002 and p = 0.048, respectively) and body-mass index (BMI) was significantly lower in control group than manganese-exposed group (p = 0.033). There was a significantly positive correlation between whole blood manganese levels and serum prolactin (r = 0.860, p < 0.001). Serum ALT levels were positively correlated with serum AST, urea and sodium (r = 0.315, p < 0.001; r = 0.121, p = 0.046; r = 0.130, p = 0.031). Serum prolactin level is a diagnostic marker for determining the effect of manganese-exposure.

Effect of manganese exposure on the reproductive organs in immature female rats.

Manganese (Mn2+) is a trace element that is essential for normal physiology, and is predominantly obtained from food. Several lines of evidence, however, demonstrated that overexposure to MnCl2 exerts serious neurotoxicity, immunotoxicity and developmental toxicity, particularly in male. The present study aimed to evaluate the effect of 0, 1.0, 3.3, and 10 mg/kg/day doses of MnCl2 on the reproductive organs in the immature female rats. Rats (PND 22; S.D. strain) were exposed to MnCl2 (MnCl2 ∙ 4H2O) dissolved in drinking water for 2 weeks. The animals were sacrificed on PND 35, then the tissues were immediately removed and weighed. Histological studies were performed using the uteri tissue samples. Serum LH and FSH levels were measured with the specific ELISA kits. Body weights of the experimental group animals were not significantly different from those of control group animals. However, ovarian tissue weights in 1 mg and 3.3 mg MnCl2 dose groups were significantly lower than those of control animals (p<0.05 and p<0.01, respectively). Uterine tissue weights of 3.3 mg dose MnCl2 groups were significantly lower than those of control animals (p<0.01), while the 1 mg MnCl2 dose and 10 mg MnCl2 dose failed to induce any change in uterine weight. Similarly, only 3.3 mg MnCl2 dose could induce the significant decrease in the oviduct weight compared to the control group (p<0.05). Non-reproductive tissues such as adrenal and kidney failed to respond to all doses of MnCl2 exposure. The uterine histology revealed that the MnCl2 exposure could affect the myometrial cell proliferation particularly in 3.3 mg dose and 10mg dose group. Serum FSH levels were significantly decreased in 1mg MnCl2 dose and 10 MnCl2 mg groups (p<0.05 and p<0.01, respectively). In contrast, treatment with 1 mg MnCl2 dose induced a significant increment of serum LH level (p<0.05). The present study demonstrated that MnCl2 exposure is capable of inducing abnormal development of reproductive tissues, at least to some extent, and altered gonadotropin secretions in immature female rats. Combined with the well-defined actions of this metal on GnRH and prolactin secretion, one can suggest the Mn2+ might be a potential environmental mediator which is involved in the female pubertal process.

The effect of manganese exposure on children's learning and memory

Manganese(Mn) is an essential element,but overexposure can lead to toxicity.Most reports focus on Mn toxicity.More and more studies have showed the main effect of Mn poisoning is the functional impairment of learning and memory.However,the infant is more sensitive to Mn exposure due to their immature organs.This review discusses children's normal blood Mn levels and requirements,and summarizes the toxic susceptibility to child and different effects of Mn during the different period exposure on children's learning and memory. Key words: Manganese exposure; Children; Learning and memory

Effect of manganese exposure and antioxidant therapy on oxidative stress in the rat brain

Manganese (Mn) is an essential element implicated in the etiologies of metal induced neurological disorders. Over‐exposure to Mn results in its accumulation in iron‐rich brain regions leading to symptoms analogous to Parkinson's disease. Mechanisms governing this response are largely undefined though it is hypothesized that Mn‐induced oxidative stress may play a role. In this study we examined weanling rats exposed to Mn (1 g/L d.i. water) for total glutathione (GSH), glutathione peroxidase (GPx) and catalase mRNA, and F2‐isoprostane (F2‐IsoP) production in the caudate putamen (CP) and hippocampus (HC). N‐acetyl‐cysteine (NAC; 200 mg/kg) or (−)‐epigallocatechin‐3‐gallate (EGCG; 5mg/kg) injections were administered to observe any protective effect against Mn‐induced oxidative stress. Mn accumulated significantly versus control in each region (p &lt; 0.05) in Mn‐exposed groups. This did not correspond to alterations in total GSH or production of F2‐IsoPs. EGCG was also associated with significant Mn accumulation in the CP (p &lt; 0.05). Significant up‐regulation of GPx gene expression (p &lt; 0.05) observed in the HC correlated with increased Mn levels, and was augmented by EGCG. These data suggest a biological response in antioxidant gene expression to Mn exposure, even in the absence of identifiable oxidative stress. Additionally, antioxidant therapy may enhance this response.

Neurobehavioral Effects of Manganese Exposure Through Inhalation and Dietary Intake in Italian Adolescents

Neurobehavioral Effects of Manganese Exposure Through Inhalation and Dietary Intake in Italian Adolescents

Effect of manganese exposure on intracellular Ca 2+ homeostasis and expression of NMDA receptor subunits in primary cultured neurons

Overexposure to manganese (Mn) has been known to induce neuronal damage. However, the mechanisms of Mn-induced neuronal cell death are incompletely understood. The objective of this study is to explore mechanisms that contribute to Mn-induced neuronal apoptosis focusing on the alteration of intracellular Ca 2+ homeostasis and expression of NMDA receptor subunits in primary cultured neurons. Treatment of neuronal cells with Mn (0–400 μM) for 6–48 h resulted in the damages of primary cultured neurons concentration- and time-dependently, which were determined by methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) release assay and supported by morphological examination. After neurons treated with Mn (25, 100, 400 μM) for 12 h, there was a significant increase in apoptosis rate [Ca 2+] i and decrease in Na +–K +-ATPase and Ca 2+-ATPase activities in a concentration-dependent manner. Moreover, Mn could inhibit expression of NMDA receptor subunits in neuron and expression of NR2A mRNA and protein were much more sensitive to Mn than those of NR1 and NR2B. In conclusion, the present results showed that Mn-induced neuronal damage by increasing [Ca 2+] i and altering expression of NMDA receptor subunits mRNAs and proteins.

The effect of manganese exposure on endogenous markers of oxidative stress in astrocytes

Manganese (Mn) is an essential trace element; however, accumulation of Mn in the brain can propagate cellular damage leading to neuronal dysfunction and symptoms analogous to neurodegenerative disorders (i.e. Parkinson's disease). Previously our lab has shown that iron deficiency significantly increases Mn accumulation decreasing glutathione (GSH) functionality. The resulting oxidative damage may alter the neuronal environment leading to dysfunction. Our goal is twofold; to characterize how Mn accumulation in astrocytes leads to lipid peroxidation (LP), and to test the efficacy of á‐tocopherol or N‐acetyl cysteine therapy in attenuating the production of F2Isoprostanes (F2Isop), a marker of LP. Primary rat astrocytes were treated with 100 or 300 ìM Mn with or without antioxidant therapy. GSH, F2Isop, and Mn levels were measured to assess overall oxidative stress. Mn exposure significantly increased GSH levels in the absence of antioxidant treatment (p&lt;0.005), though no difference in GSH was seen in any antioxidant treatment compared to control. Significant increases in F2Isop (p&lt;0.05) were present in Mn treated cells and attenuated by antioxidant pretreatment. These data imply that Mn induced LP is due to alterations in the GSH protective system, but may be mitigated by antioxidant therapy.Funded by NINDS 1R15NS061309‐01