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Hippocampal expression of myelin-associated inhibitors is induced with age-related cognitive decline and correlates with deficits of spatial learning and memory.

Abstract：

: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 (12-13 months) and aged (26-28 months) Fischer 344 × Brown Norway rats. Rats were behaviorally phenotyped by Morris water maze testing and classified as aged cognitively intact (n = 7-8) or aged cognitively impaired (n = 7-10) relative to adults (n = 5-7). 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.

journal_name

J Neurochem

journal_title

Journal of neurochemistry

authors

Vanguilder HD,Bixler GV,Sonntag WE,Freeman WM

doi

10.1111/j.1471-4159.2012.07671.x

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

77-98

issue

eissn

0022-3042

issn

1471-4159

journal_volume

121

pub_type

杂志文章

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Hippocampal expression of myelin-associated inhibitors is induced with age-related cognitive decline and correlates with deficits of spatial learning and memory.