myelin-basic-protein and Lead-Poisoning

Lead (Pb) poisoning has always been a serious health concern, as it permanently damages the central nervous system. Chronic Pb accumulation in the human body disturbs oligodendrocytes (OLs) differentiation, resulting in dysmyelination, but the molecular mechanism remains unknown. In this study, Pb at 1 μM inhibits OLs precursor cells (OPCs) differentiation via decreasing the expression of Olig 2, CNPase proteins in vitro. Moreover, Pb treatment inhibits the sodium/calcium exchanger 3 (NCX3) mRNA expression, one of the major means of calcium (Ca(2+)) extrusion at the plasma membrane during OPCs differentiation. Also addition of KB-R7943, NCX3 inhibitor, to simulate Pb toxicity, resulted in decreased myelin basic protein (MBP) expression and cell branching. Ca(2+) response trace with Pb and KB-R7943 treatment did not drop down in the same recovery time as the control, which elevated intracellular Ca(2+) concentration reducing MBP expression. In contrast, over-expression of NCX3 in Pb exposed OPCs displayed significant increase MBP fluorescence signal in positive regions and CNPase expression, which recovered OPCs differentiation to counterbalance Pb toxicity. In conclusion, Pb exposure disturbs OLs differentiation via affecting the function of NCX3 by inducing intracellular calcium overload.

Topics: Calcium; Cell Differentiation; Down-Regulation; Humans; Lead Poisoning; Myelin Basic Protein; Oligodendroglia; RNA, Messenger; Sodium-Calcium Exchanger; Thiourea

An expanded follow-up assessment of the autoantibody response to neuronal and astroglial autoantigens (NF68; NF160; NF200; MBP; GFAP) as early markers of neurotoxicity was performed in male workers exposed to lead (Pb) of a battery factory (n=50) and a matched reference group (R) of workers at a food packing plant (n=39). Mean age, years of exposure and blood lead (PbB ug/dl) (+/-SD) for lead and R, respectively, were: Age:39 +/- 6; 41 +/- 7; Yrs. Exposed: 14 +/- 6:0; PbB: 32 +/- 11: 16 +/- 5 percent with detectable titers to nervous system proteins in the Pb and R populations, respectively, were: Anti-NF68: 59; 17; Anti-NF160: 28; 15; Anti-NF200: 25; 0; Anti-GFAP: 90; 20; Anti-MBP: 16; 4. Autoantibodies to nervous system proteins predominated in workers occupationally exposed to Pb compared to R. Anti-NF68 and GFAP titers were the most frequently encountered. Anti-NF68 titers were significantly correlated with years of exposure (r = 0.538, p < 0.0001) and with PbB (r=0.325, p < 0.05). Furthermore, the number of detectable autoantibody types correlated with clinical scores of sensorimotor deficits (r = 0.459, p < 0.0001). This study suggests that autoantibodies provide a promising biomarker of neurotoxicity while providing information on subcellular targets. It also raises concerns of toxicant-induced autoimmune neuropathy.

Topics: Adult; Air Pollutants, Occupational; Autoantibodies; Biomarkers; Case-Control Studies; Egypt; Environmental Monitoring; Epidemiological Monitoring; Follow-Up Studies; Glial Fibrillary Acidic Protein; Humans; Immunoglobulin G; Immunoglobulin M; Inhalation Exposure; Lead Poisoning; Male; Middle Aged; Myelin Basic Protein; Occupational Diseases; Occupational Exposure; Peripheral Nervous System Diseases; Sensitivity and Specificity; Surveys and Questionnaires; Threshold Limit Values; Urban Health

Postnatal exposure of rats to lead has been shown previously to cause CNS hypo-myelination. Since rats intoxicated with lead often show retarded growth, the superimposed malnutrition, which as such can cause hypomyelination, may contribute to myelin deficit. In the present study control rats and lead exposed rats which did not have any retardation of growth were examined by radioimmunological assay of myelin basic protein (MBP) of homogenates of cerebrum and cerebellum at 30, 60 and 120 days of age. Lead was administered on postnatal days 1-15 by daily intraperitoneal injections of 10 mg lead nitrate/kg body weight. This lead dose results in light microscopically discernible hemorrhagic encephalopathy in the cerebellum of 15-day old rats, but does not induce growth retardation (Sundström et al. 1983). The controls were injected with vehicle only. The amount of lead in the blood and brain homogenates of lead-exposed and control rats 15-200 days old was estimated by atomic absorption spectrophotometry. Significant differences between the lead-exposed and control rats were not found in the cerebral or cerebellar content of MBP. Considering the results of previous investigations, the findings do not exclude a hypo-myelinating effect of lead, but they suggest that exposure to lead without concomitant malnutrition does not cause hypo-myelination in the cerebrum and cerebellum of the developing rat.

Topics: Aging; Animals; Body Weight; Brain; Brain Chemistry; Electrophoresis, Polyacrylamide Gel; Immunosorbent Techniques; Lead; Lead Poisoning; Male; Myelin Basic Protein; Organ Size; Radioimmunoassay; Rats; Rats, Inbred Strains; Time Factors

An experimental model of subacute lead and benzene intoxication was induced in rabbits. It increased significantly delta-aminolevulinic acid (14C-ALA) incorporation into CNS myelin. ALA stably fixes on myelin proteins, especially Wolfgram proteins. In spite of this about one half of ALA incorporated into myelin linked with its basic proteins. Lead and benzene intoxication cause changes in the proportion of the basic fractions of myelin proteins. The amount of basic proteins increases, while the amount of proteolipid and Wolfgram proteins decreases. Lead and especially benzene intoxication decreases exogenous ALA insertion into basic proteins and proteolipid proteins, with ALA fixation on Wolfgram proteins remaining unchanged.

Topics: Aminolevulinic Acid; Animals; Benzene; Lead Poisoning; Levulinic Acids; Male; Myelin Basic Protein; Myelin Proteins; Rabbits

The effects of chronic lead intoxication were studied by examining the optic nerve of mice given lead-containing mother's milk from day 1 to day 21 of life. Biochemical assays for myelin basic protein, 2',3'-cyclic nucleotide phosphodieterase, and cerebroside sulfotransferase showed that the total amount of myelin produced by the lead-exposed animals was decreased. Lead exposure did not alter the number of oligodendroglia or the relationship between axons and myelin sheaths. The hypomyelination was paralleled by a reduction in size of optic axons in the lead-exposed animals. The data suggest that chronic exposure to lead in developing mice results in a primary effect on neurons and that hypomyelination is secondary to reduction in axon size.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Age Factors; Animals; Behavior, Animal; Cerebrosides; Female; Lead Poisoning; Maternal-Fetal Exchange; Mice; Myelin Basic Protein; Optic Nerve; Organ Size; Pregnancy; Sulfotransferases; Sulfurtransferases