Neural stem cell- and neurogenesis-related gene expression profiles in the young and aged dentate gyrus

Abstract

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 NFkappaB 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.

Chronic Oxidative Stress, Mitochondrial Dysfunction, Nrf2 Activation and Inflammation in the Hippocampus Accompany Heightened Systemic Inflammation and Oxidative Stress in an Animal Model of Gulf War Illness

“…We employed the manufacturer’s instructions, as previously detailed (Shetty et al, 2013). The concentration and quality of the RNA were determined by a Nanodrop spectrophotometer, using A260 and A260:A280 values, respectively (ThermoFisher Scientific, Wilmington, DE, United States).…”

“…A previously described (Shetty et al, 2013) qRT-PCR protocol was used. In brief, template cDNA (102 μl) from each hippocampal sample was mixed with 1,350 μl of 2X RT 2 qPCR master mix (SABiosciences, Qiagen, Valencia, CA, United States) and 1,248 μl of dH 2 O to obtain a cocktail of 2,700 μl.…”

Preserved neurogenesis in non-demented individuals with AD neuropathology

“…Indeed a growing body of literature has emerged demonstrating a strong correlation between neurogenesis, memory and cognitive function in animal models. Notably, promotion of adult hippocampal neurogenesis is associated with improved spatial memory, while a decline in neurogenesis underlies cognitive impairments reportedly associated with aging, trauma and various neurodegenerative disorders including AD1112131415.…”

Differentiation of stem cells derived from carious teeth into dopaminergic‐like cells

“…Studies reveal that the suppression of this gene leads to the prolongation of the entire cell cycle length particularly in the G2 to M phase entry. Subsequently, this contributes to compromised neural progenitor proliferation and differentiation (Vance & Hayashi 2010, Lian et al 2012, Shetty et al 2013. Perhaps, this could explain the downregulation of cell cycle markers such as EP300, HDAC4, APOE and MDK despite them being supplied with a nutrient-rich chemically defined media (Borsini et al 2015).…”