Abstract
The known effects of aging on the brain and behavior include impaired cognition, increases in anxiety and depressive-like behaviors, and reduced locomotor activity. Environmental exposures and interventions also influence brain functions during aging. We investigated the effects of normal aging under controlled environmental conditions and in the absence of external interventions on locomotor activity, cognition, anxiety and depressive-like behaviors, immune function and hippocampal gene expression in C57BL/6 mice. Healthy mice at 4, 9, and 14 months of age underwent behavioral testing using an established behavioral battery, followed by cellular and molecular analysis using flow cytometry, immunohistochemistry, and quantitative PCR. We found that 14-month-old mice showed significantly reduced baseline locomotion, increased anxiety, and impaired spatial memory compared to younger counterparts. However, no significant differences were observed for depressive-like behavior in the forced-swim test. Microglia numbers in the dentate gyrus, as well as CD8+ memory T cells increased towards late middle age. Aging processes exerted a significant effect on the expression of 43 genes of interest in the hippocampus. We conclude that aging is associated with specific changes in locomotor activity, cognition, anxiety-like behaviors, neuroimmune responses and hippocampal gene expression.
Highlights
Aging is a known risk factor for degenerative changes in various brain regions [1,2], which, in turn, results in functional loss, such as progressive decline in learning, memory, and cognitive and motor functions [3,4,5,6,7,8,9,10]
Aging alone is not the only risk factor and other extrinsic and intrinsic factors may play a role in the impairment of brain functions during normal aging [20,21,22,23,24]
A significant increase in anxiety-like behavior and a decrease in spatial memory was observed in 14-month-old mice compared to 4-month-old mice, which suggests that age is a controlling factor for the onset of anxiety and memory impairment
Summary
Aging is a known risk factor for degenerative changes in various brain regions [1,2], which, in turn, results in functional loss, such as progressive decline in learning, memory, and cognitive and motor functions [3,4,5,6,7,8,9,10]. Studies in the past have shown a significant increase in anxiety [11,12,13,14] and depressive-like [13,15] behaviors, and decline in spatial learning and memory [11,16,17,18,19] and locomotion [12,13] in aging C57BL/6 mice, 12 month onwards. The dysfunctional glial cells mediate immune reactivity and inflammation by
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