期刊
JOURNAL OF NEUROCHEMISTRY
卷 121, 期 1, 页码 77-98出版社
WILEY
DOI: 10.1111/j.1471-4159.2012.07671.x
关键词
Fischer 344 Brown Norway rat; Morris water maze; myelin-associated glycoprotein; neurite outgrowth inhibitor A; Nogo-66 receptor; oligodendrocyte myelin glycoprotein
资金
- NIA [R01AG026607, P01AG11370]
- Donald W. Reynolds Foundation
Impairment of cognitive functions including hippocampus-dependent spatial learning and memory affects nearly half of the aged population. Age-related cognitive decline is associated with synaptic dysfunction that occurs in the absence of neuronal cell loss, suggesting that impaired neuronal signaling and plasticity may underlie age-related deficits of cognitive function. Expression of myelin-associated inhibitors (MAIs) of synaptic plasticity, including the ligands myelin-associated glycoprotein, neurite outgrowth inhibitor A, and oligodendrocyte myelin glycoprotein, and their common receptor, Nogo-66 receptor, was examined in hippocampal synaptosomes and Cornu ammonis area (CA)1, CA3 and dentate gyrus subregions derived from adult (1213 months) and aged (2628 months) Fischer 344 x Brown Norway rats. Rats were behaviorally phenotyped by Morris water maze testing and classified as aged cognitively intact (n = 78) or aged cognitively impaired (n = 710) relative to adults (n = 57). MAI protein expression was induced in cognitively impaired, but not cognitively intact, aged rats and correlated with cognitive performance in individual rats. Immunohistochemical experiments demonstrated that up-regulation of MAIs occurs, in part, in hippocampal neuronal axons and somata. While a number of pathways and processes are altered with brain aging, we report a coordinated induction of myelin-associated inhibitors of functional and structural plasticity only in cognitively impaired aged rats. Induction of MAIs may decrease stimulus-induced synaptic strengthening and structural remodeling, ultimately impairing synaptic mechanisms of spatial learning and memory and resulting in cognitive decline.
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