Neuroplasticity in old age: Sustained fivefold induction of hippocampal neurogenesis by long‐term environmental enrichment

Abstract

Neurons are continually born from endogenous stem cells and added to the dentate gyrus throughout life, but adult hippocampal neurogenesis declines precipitously with age. Short-term exposure to an enriched environment leads to a striking increase in new neurons, along with a substantial improvement in behavioral performance. Could this plastic response be relevant for explaining the beneficial effects of leading "an active life" on brain function and pathology? Adult hippocampal neurogenesis in mice living in an enriched environment from the age of 10 to 20 months was fivefold higher than in controls. Relatively, the increase in neuronal phenotypes was entirely at the expense of newly generated astrocytes. This cellular plasticity occurred in the context of significant improvements of learning parameters, exploratory behavior, and locomotor activity. Enriched living mice also had a reduced lipofuscin load in the dentate gyrus, indicating decreased nonspecific age-dependent degeneration. Therefore, in mice signs of neuronal aging can be diminished by a sustained active and challenging life, even if this stimulation started only at medium age. Activity exerts not only an acute but also a sustained effect on brain plasticity.

Can endocrine disruptors influence neuroplasticity in the aging brain?

“…Environmental enrichment has been known for five decades to nurture early brain development. Kempermann et al (2002) observed a dramatic increase in new neurons in mice 10 months of age living in a typical enriched environment for rodents (playmates and toys) for 10 months. Moreover, their performance on a battery of behavioral assays also exceeded those of the controls housed under standard conditions.…”

Epigenetic regulation of aging stem cells

“…For example, reducing circulating levels of corticosteroids in adult rats by adrenalectomy has been shown to restore neural progenitor proliferation and neurogenesis (Cameron and McKay, 1999) and increasing the declining levels of insulin growth factor 1 (IGF-1) in aged rodents promotes adult neurogenesis and stem-celldependent muscle regeneration (Lichtenwalner et al, 2001;Musaro et al, 2004). In further support of reversible alterations to stem cell function in some tissues, changes in external stimuli, such as exposure to an enriched social environment (Kempermann et al, 1998b(Kempermann et al, , 2002 or physical exercise (Kronenberg et al, 2006;Lugert et al, 2010), improve age-related declines in NSC proliferation and neurogenesis. Taken together, Figure 1 Mechanisms of stem cell aging.…”

Optimization of multiplexed bead-based cytokine immunoassays for rat serum and brain tissue

“…We initially used a standard strategy for processing brain tissue for immunohistochemical analyses of inflammatory markers Kraig, 1996 , 1998;. However in these preliminary studies, animals from a modestly enriched environment had corticosterone levels of 150 ± 25 ng/ml (n = 9), values that might be more consistent with stress (Diamond et al, 1992) than with environmental enrichment (Kempermann et al, 2002;Kraig et al, 2003) (Fig. 1).…”

“…As a result, we changed our harvest procedures to a group-anesthesia format that would be conducive for use with animals housed as a group in typical environmental enrichment paradigms (Kempermann et al, 2002;Kraig et al, 2003). Animals harvested using this protocol had serum corticosterone levels of 62 ± 4 ng/ml (n = 9), values that while elevated from normal are consistent with environmental enrichment (Kempermann et al, 2002;Kraig et al, 2003). This is more than a two-fold and significant (P < 0.007, Mann-Whitney rank sum) decrease in mean corticosterone level and nearly a six-fold drop in variance.…”