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 increasing interests of importance. We investigated the effects of low-level Pb on the brain in a normal condition and a pathophysiological condition of energy shortage that is commonly found in age-related neurological diseases. Middle-aged rats (15 months old) were exposed to 200 mg/l Pb acetate in drinking water for 2 months and thereafter received bilateral intracerebroventricular injections of streptozotocin (STZ). After 1 month's additional exposure to the same level of Pb solution as before the rats were sacrificed. Blood and brain Pb levels were measured by graphite furnace atomic absorption spectrophotometry. Energy-rich phosphate levels in the brain were determined by high-performance liquid chromatography equipped with a UV detector. Astroglial activation and glucose-regulated protein (GRP)94 expression were examined immunohistochemically. Exposure to Pb increased the blood Pb level to 10.8 microg/dl and the brain Pb level to 0.052 microg/g. But a significant additional increase in the brain Pb level, to 0.101 microg/g, became obvious in rats treated with Pb + STZ. Both Pb and STZ induced perturbation in brain energy metabolism, but no further alteration in energy metabolite levels was found in rats treated with Pb + STZ. Astroglial activation and GRP94-positive astrocytes and neurons were found only in the brains of Pb + STZ-treated rats. These results suggest that exposure to low-level Pb can perturb brain energy metabolism and the brain becomes more vulnerable to Pb when it is under energy stress.
Department of Pathochemistry and General Neurochemistry, University of Heidelberg, Heidelberg, Germany.
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SW
Yun
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U
Gärtner
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T
Arendt
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S
Hoyer
D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects*; D003401:Creatine / Q000032:analysis; D004734:Energy Metabolism / Q000187:drug effects*; D006153:Guanosine Diphosphate / Q000032:analysis; D006160:Guanosine Triphosphate / Q000032:analysis; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D007276:Injections, Intraventricular; D007854:Lead / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D010725:Phosphocreatine / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000008:administration & dosage
D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; C018551:glucose-regulated proteins; D010725:Phosphocreatine; D006153:Guanosine Diphosphate; D007854:Lead; D013311:Streptozocin; D000244:Adenosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D003401:Creatine