Increase in vulnerability of middle-aged rat brain to lead by cerebral energy depletion

The neurotoxic effects of low-level lead (Pb) during senescence are increas ing interests of importance. We investigated the effects of low-level Pb on the brain in a normal condition and a pathophysiological condition of ener gy shortage that is commonly found in age-related neurological diseases. Mi ddle-aged rats (15 months old) were exposed to 200 mg/l Pb acetate in drink ing water for 2 months and thereafter received bilateral intracerebroventri cular injections of streptozotocin (STZ), After 1 month's additional exposu re to the same level of Pb solution as before the rats were sacrificed. Blo od and brain Pb levels were measured by graphite furnace atomic absorption spectrophotometry. Energy-rich phosphate levels in the brain were determine d by high-performance liquid chromatography equipped with a UV detector. As troglial activation and glucose-regulated protein (GRP)94 expression were e xamined immunohistochemically. Exposure to Pb increased the blood Pb level to 10.8 mu g/dl and the brain Pb level to 0.052 mu g/g, But a significant a dditional increase in the brain Pb level, to 0.101 mu g/g, became obvious i n rats treated with Pb + STZ. Both Pb and STZ induced perturbation in brain energy metabolism, but no further alteration in energy metabolite levels w as found in rats treated with Pb + STZ, Astroglial activation and GRP94-pos itive astrocytes and neurons were found only in the brains of Pb + STZ-trea ted rats. These results suggest that exposure to low-level Pb can perturb b rain energy metabolism and the brain becomes more vulnerable to Pb when it is under energy stress. (C) 2000 Elsevier Science Inc.