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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
Author(s) -
VanGuilder Heather D.,
Bixler Georgina V.,
Sonntag William E.,
Freeman Willard M.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07671.x
Subject(s) - neuroscience , hippocampal formation , morris water navigation task , dentate gyrus , hippocampus , myelin , synaptic plasticity , psychology , cognitive decline , neuroplasticity , radial arm maze , biology , cognition , central nervous system , medicine , receptor , working memory , dementia , disease
J. Neurochem. (2012) 121 , 77–98. 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.