147,148 Stimuli that entail an increase in neuronal activity have

147,148 Stimuli that entail an increase in neuronal activity have been shown to stimulate neurogenesis and enhance survival of new neurons in the adult mammalian hippocampus.149 The incorporation of functional adult-generated neurons into existing neural networks provides higher capacity for plasticity, while they favor the encoding and storage of certain types of memories.150-152 Although neurogenesis continues throughout life, its rate declines with increasing age,153,154 and the proportion of Inhibitors,research,lifescience,medical neuronal stem cells that survive to become mature neuronal ceils is reduced.155 This

may be due to intrinsic decline in neuronal stem cell responsiveness to stimulating environmental cues, to a decrease in or disappearance of these environmental cues, or to accumulation of inhibitory factors.156 Intrinsic properties of neural progenitor cells such as gene transcription and telomere activity change with age, Inhibitors,research,lifescience,medical which may contribute to decline in neurogenesis. While most studies indicated a correlation between decreased Inhibitors,research,lifescience,medical hippocampal neurogenesis and impaired performance in hippocampus-dependent ATM Kinase Inhibitor cognitive tasks in age mice, few have demonstrated that young and aged mice are equivalent in their cognitive ability. The lack of neuronal ability to divide may be overcome by replacing damaged neurons or

by restoring their function. Thus, Kittappa et al157 revisited the molecular mechanisms responsible for neuronal renewal from stem cells, which are present in specific niches within the adult brain. The authors provided the novel notion that even non-terminaliy Inhibitors,research,lifescience,medical differentiated neural stem cells play roles in the regeneration of neurons and their synaptic Inhibitors,research,lifescience,medical function by mechanisms beyond mere cell replacement. These cells signal specific survival pathways that are worth investigating

in search for novel therapeutic strategies against neurodegeneration. According to this notion, noninvasive tools to follow up synaptic function in the living brain are therefore essential for our better understanding of neuronal regeneration. Although neuronal turnover is reduced in every neurogenic region of the aged brain, neuronal precursor cells clearly survive, remain responsive to growth factors and other physiological Nature Methods stimuli, and can increase their activity in response to damage.157 Exploration of the regulation of neuronal progenitor cells in the aging brain is critical not only for understanding age-related cognitive deficits, but also for progress toward the goal of using the brain’s regenerative potential to restore functional loss. Dysregulated or impaired neurogenesis may compromise plasticity and neuronal function in the hippocampus and other neuronal systems, and exacerbate neuronal vulnerability.

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