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

Department of Pharmacology, R130, Hershey Center for Applied Research, Penn State College of Medicine, Hershey, PA 17033, USA.
Journal of Neurochemistry (Impact Factor: 4.24). 01/2012; 121(1):77-98. DOI: 10.1111/j.1471-4159.2012.07671.x
Source: PubMed

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.

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    Neurochemical Research 12/2014; 40(3). DOI:10.1007/s11064-014-1491-z · 2.55 Impact Factor
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    Cellular and Molecular Neurobiology 07/2014; 34(8). DOI:10.1007/s10571-014-0088-z · 2.20 Impact Factor
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    ABSTRACT: Background The aim of this study was to investigate the effects of a potent nitric oxide-guanylate cyclase activator, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), on learning and memory functions in aged rats. Material and Methods Rats were divided into 2 groups as 4-month-old and 24-month-old rats. Rats received YC-1 (1 mg/kg/day) for 2 weeks long-term. Morris water maze (MWM) and passive avoidance (PA) tests were used to determine learning and memory functions. Results In the MWM test, there is a significant increase in the acquisition latency (1-4 days) of 24-month-old rats. There is a significant reduction in the "time spent in the escape platform's quadrant" in 24-month-old rats compared to 4-month-old rats in the probe trial of the MWM test. YC-1 treatment reversed the reduction of the "time spent in the escape platform's quadrant" of 24-month-old rats. In the PA test, there was no significant difference in the 1st-day latency of rats in all groups. On the 2nd day, retention latency significantly decreased in the 24-month-old rats compared to 4-month-olds. YC-1 reversed the diminished retention latency in 24-month-old rats. YC-1 treatment and aging did not affect results of the locomotor activity test or the foot-shock sensitivity test, suggesting our results were not due to a change in motor activity or disability of the animals. Conclusions Our findings suggest that activation of the NO-sGC-cGMP pathway plays an important role in spatial and emotional learning and memory functions in aged rats.
    08/2014; 20:130-137. DOI:10.12659/MSMBR.891064


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