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.
Yun
S W
SW
Department of Pathochemistry and General Neurochemistry, University of Heidelberg, Heidelberg, Germany.
Gärtner
U
U
Arendt
T
T
Hoyer
S
S
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