Neural stem cell- and neurogenesis-related gene expression profiles in the young and aged dentate gyrus
Hippocampal neurogenesis, important for memory and mood function, wanes greatly in old age. Studies in rat models have implied that this decrease is not due to loss of neural stem cells (NSCs) in the subgranular zone of the dentate gyrus (DG) but rather due to an increased quiescence of NSCs. Additional studies have suggested that changes in the microenvironment, particularly declines in the concentrations of neurotrophic factors, underlie this change. In this study, we compared the expression of 84 genes that are important for NSC proliferation and neurogenesis between the DG of young (4 months old) and aged (24 months old) Fischer 344 rats, using a quantitative real-time polymerase chain reaction array. Interestingly, the expression of a vast majority of genes that have been reported previously to positively or negatively regulate NSC proliferation was unaltered with aging. Furthermore, most genes important for cell cycle arrest, regulation of cell differentiation, growth factors and cytokine levels, synaptic functions, apoptosis, cell adhesion and cell signaling, and regulation of transcription displayed stable expression in the DG with aging. The exceptions included increased expression of genes important for NSC proliferation and neurogenesis (Stat3 and Shh), DNA damage response and NF-kappaB signaling (Cdk5rap3), neuromodulation (Adora1), and decreased expression of a gene important for neuronal differentiation (HeyL). Thus, age-related decrease in hippocampal neurogenesis is not associated with a decline in the expression of selected genes important for NSC proliferation and neurogenesis in the DG.
KeywordsAging Hippocampus Dentate gyrus Dentate neurogenesis Genes Gene expression Hippocampal neurogenesis Neural stem cells Stem cells and aging qRT-PCR
This research was supported by Emerging Technology Funds (from the Texas A&M Health Science Center to A.K.S.) and grants from the National Institutes of Health (NS054780 and AG20924 to A.K.S.) and Department of Veterans Affairs (VA Merit Review Award to A.K.S.). We thank Dr. Bing Shuai for his excellent contribution to tissue harvesting.
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