Nutrition, neurotoxicants and age-related neurodegeneration.
The National Institute on Aging supports a program of investigation of "biomarkers" of aging (biological parameters that change in magnitude with age), some of which may be among the, as yet unknown, causes of Alzheimer's disease. Exposure to neurotoxicants can also produce symptoms similar to Alzheimer's disease and has been proposed as a causative factor. We have examined the role of dietary factors and age on Alzheimer's disease-like neurohistological and behavioral symptoms as well as on the neurochemical effects of treatment with a prototypical neurotoxicant, trimethyltin (TMT). We found that aging greatly increased the susceptibility of hippocampal neurons to TMT-induced neurodegeneration. Limiting the dietary intake of calories, which has been reported to slow the aging process, also reduced the neurotoxic effects of a given dose of TMT. Our current research focuses on the use of neurotoxins to model neurodegenerative conditions of aging in animals. We propose that by identifying an age-amplified biomarker or biomarkers somewhere along the chain from neurotoxic stimulus to neuronal necrosis we may also discover an up- or down-regulated gene, via it's gene product, that contributes to the etiology of human dementias. Our preliminary data suggest that up-regulated synthesis of post-synaptic glutamate receptors of the kainic acid-preferring subtype may be such a biomarker.
Matthews
J C
JC
Department of Pharmacology, School of Pharmacy, University of Mississippi, University 38677.
Scallet
A C
AC
D000375:Aging / Q000502:physiology*; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced*; D004032:Diet / Q000009:adverse effects*; D004044:Dietary Proteins / Q000494:pharmacology; D002149:Energy Intake; D006624:Hippocampus / Q000187:drug effects*; D007608:Kainic Acid / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012307:Risk Factors; D014298:Trimethyltin Compounds / Q000633:toxicity*
D000596:Amino Acids; D004044:Dietary Proteins; D014298:Trimethyltin Compounds; D007608:Kainic Acid