The effects of mitochondrial failure upon cholinergic toxicity in the nucleus basalis.
Increased glutamate or acetylcholine receptor stimulation may interact with mitochondrial failure to increase the vulnerability of cholinergic neurons within the nucleus basalis. Understanding of the mechanisms that underlie this vulnerability may lead to a therapy to prevent the degeneration of these neurons in Alzheimer's disease. In the presence of a mitochondrial energy deficit, excess stimulation of N-methyl-D-aspartate (NMDA) receptors was not required for cytotoxicity. Furthermore, stimulation of cholinergic receptors was cytotoxic to cholinergic neurons but this toxicity was not enhanced by NMDA stimulation. Chronic administration of NMDA antagonists, such as memantine, amantadine or MK-801, attenuated the effects of mitochondrial failure in the presence or absence of excessive cholinergic or NMDA receptor stimulation.
Wenk
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GL
Arizona Research Laboratories, Division of Neural Systems, Memory and Aging, University of Arizona, Tucson 85724, USA.
Danysz
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W
Roice
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DD
D000109:Acetylcholine / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D008297:Male; D008559:Memantine / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D013377:Substantia Innominata / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D016194:Receptors, N-Methyl-D-Aspartate; D013385:Succinate Dehydrogenase; D000109:Acetylcholine; C015392:3-nitropropionic acid; D008559:Memantine