Abstract
Despite the great increase in human lifespan with improved medical care, the physiological and pathological changes such as memory and cognitive disorders and associated anxiety and depression are major concern with aging. Molecular mechanisms underlying these changes are little known. The present study examined the differentially expressed genes (DEGs) and the genes with differentially expressed isoforms in three brain regions, anterior cingulate cortex (ACC), amygdala and hippocampus, throughout the lifespan of mice. Compared to 2-month old mice, both 12- and 24-month old mice displayed memory and cognitive impairments in the Morris water maze, Y-maze, and novel object recognition tests and depression- and anxiety-like behaviors in the tail suspension, forced swimming, open field, and elevated plus maze tests. RNA sequencing analysis identified 634 and 1078 DEGs in ACC, 453 and 1015 DEGs in the amygdala and 884 and 1054 DEGs in hippocampus in the 12- and 24-month old mice, respectively. Similarly, many genes with differentially expressed isoforms were also identified in these three brain regions in the 12- and 24-month old mice. Further functional analysis revealed that many DEGs and the genes with differentially expressed isoforms in the ACC and amygdala were mapped to depression- and anxiety-related genes, respectively and that a lot of DEGs and the genes with differentially expressed isoforms in hippocampus were mapped to cognitive dysfunction-related genes from both 12- and 24-month old mice. All of these mapped DEGs and the genes with differentially expressed isoforms were closely related to neuroinflammation. Our findings indicate that these neuroinflammation-related DEGs and the genes with differentially expressed isoforms are likely new targets in the management of memory/cognitive impairment and emotional disorders during the aging.
Highlights
With rapid socio-economic development, the life expectancy of human being is increasing (Beard et al, 2016)
To better understand the network of gene changes in the anterior cingulate cortex (ACC), hippocampus and amygdala with aging, the present study focused on gene expression that changed in these three brain regions throughout the lifespan of mice
Bioinformatical analyses further showed that all differentially expressed genes (DEGs) and the genes with differentially expressed isoforms identified in ACC, hippocampus and amygdala of two groups of aging mice were closely related to the neuro-inflammation
Summary
With rapid socio-economic development, the life expectancy of human being is increasing (Beard et al, 2016) Agerelated disorders such as Alzheimer’s disease (AD) and dementia afflict vast majority of aged patients and become most significant public health issues and considerable challenges around the world (Kanasi et al, 2016). Cognitive and functional impairment as the hallmark of aging is often emphasized, neuropsychiatric symptoms are directly responsible for the reduced quality of life and the increased rates of disability in patients and their families. Current treatments for these age-related disorders are unsatisfactory and/or produce adverse effects at least in part due to incomplete understanding of molecular mechanisms underlying these disorders. Identifying the differentially expressed genes (DEGs) in the cognitive impairment-, depression-, or anxiety-associated brain regions of aging mice is a key step for searching new targets for novel treatments and preventative tactics for the age-related disorders
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