Myelin glycoproteins targeted by lead in the rodent model of prolonged exposure

The aim of these experiments was to discern whether prolonged exposure of rats to lead (Pb) in water, as occurs in typical environmental exposure, affects the structure of myelin in the brain, the protein levels of the myelin glycoproteins myelin associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG). During chronic lead intoxication, Pb levels in myelin fractions significantly increases. Prolonged lead exposure was found to decrease the expression of both MAG and MOG to a similar degree (80-85% of control values). Additionally, the electron microscopic studies have indicated the existence of structural changes in the axonal myelin sheath by revealing disintegration of its multilamellar structure. These morphological disturbances in Pb-intoxicated rats were paralleled by changes in myelin membrane fluidity as measured by spectrofluorometry and electron paramagnetic resonance (EPR) techniques employing a fatty acid spin label. In Pb-treated rats, enhanced membrane fluidity was observed, as indicated both by decreased anisotropy of the membrane and decreased order parameter. These results suggest that Pb influences the integrity of the myelin sheath in brain of adult rats and decreased level of both glycoproteins may significantly contribute to that effect.