The glial drug methionine sulfoximine reduces goldthioglucose lesions in mice.
A toxic form of glucose, goldthioglucose (GTG), damages the arcuate nucleus and nucleus of the solitary tract (NTS) after passage through permeable circumventricular capillaries in adjacent structures, but the mechanism of action is unclear. To see if GTG initially acts upon glia to cause lesions, adult male mice were given either saline or a drug--methionine sulfoximine (MS)--that causes glia, but not neurons, to generate intracellular deposits of glycogen from glutamate. One day later, mice were given 0.3 mg/g of GTG and the subsequent severity of GTG-induced arcuate and NTS lesions was examined. The MS-treated group had significantly smaller GTG lesions in both brain sites, suggesting that a MS-induced alteration in glial metabolism produced a diminished uptake of GTG. Uptake of GTG via a glial glucose transport system may lead to lesions by disturbing the heme metabolism of a specialized subset of glia present in these regions. Factors affecting glial glucose transport in these areas may thus modulate both effects of GTG and effects of glucose upon the regulation of feeding.
Young
J K
JK
Department of Anatomy, Howard University, Washington, DC 20059.
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006051:Aurothioglucose / Q000633:toxicity*; D006003:Glycogen / Q000378:metabolism*; D006046:Gold / Q000633:toxicity*; D006651:Histocytochemistry; D007501:Iron / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008717:Methionine Sulfoximine / Q000494:pharmacology*; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*
D008717:Methionine Sulfoximine; D006051:Aurothioglucose; D006046:Gold; D006003:Glycogen; D007501:Iron