Abstract
The aging brain presents a general decline in plasticity that also affects hippocampal neurogenesis. Besides the well-known reduction in the rate of neuronal generation, development of new neurons is largely delayed in the aging brain. We have recently shown that this slow development is accelerated when middle-aged mice perform voluntary exercise in a running wheel. It is unclear whether the effects of exercise on neurogenic plasticity are persistent in time in a manner that might influence neuronal cohorts generated over an extended time span. To clarify these issues, we examined the effects of exercise length in 3-week-old neurons and found that their development is accelerated only when running occurs for long (3–4 weeks) but not short periods (1 week). Furthermore, chronic running acted with similar efficiency on neurons that were born at the onset, within, or at the end of the exercise period, lasting until 3 months. Interestingly, no effects were observed on neurons born 1 month after exercise had ended. Our results indicate that multiple neuronal cohorts born throughout the exercise span integrate very rapidly in the aging brain, such that the effects of running will accumulate and expand network assembly promoted by neurogenesis. These networks are likely to be more complex than those assembled in a sedentary mouse due to the faster and more efficient integration of new neurons.
Highlights
The generation of new neurons in the adult hippocampus, a region of the brain involved in spatial navigation and memory formation (Buzsaki and Moser, 2013), is a striking form of plasticity that persists throughout life in several species including humans (Altman and Das, 1965; Eriksson et al, 1998; Moreno-Jiménez et al, 2019)
We have previously shown that running accelerates development and functional integration of new granule cells (GCs) in the aging hippocampus (Trinchero et al, 2017)
New neuronal cohorts were labeled in middle-aged mice (8 months of age; 8M) using a retrovirus expressing GFP (RV-GFP)
Summary
The generation of new neurons in the adult hippocampus, a region of the brain involved in spatial navigation and memory formation (Buzsaki and Moser, 2013), is a striking form of plasticity that persists throughout life in several species including humans (Altman and Das, 1965; Eriksson et al, 1998; Moreno-Jiménez et al, 2019). Aging affects many functions in the brain including synaptic transmission and plasticity, which are thought to contribute to memory loss (Burke and Barnes, 2006; Fan et al, 2017). Given that the hippocampus is vulnerable to age-related alterations and neurodegeneration, finding strategies to enhance plasticity in this structure becomes relevant to prevent or alleviate the effects of senescence (Bartsch and Wulff, 2015). One of the direct benefits may arise from the activity-dependent
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