Marked species and age‐dependent differences in cell proliferation and neurogenesis in the hippocampus of wild‐living rodents

Abstract

Variations in the extent of adult neurogenesis and natural and experimental factors controlling it have been described in laboratory animals. The wide range of variation seen even within a species, the mouse, raises the question as to which rates of neurogenesis can be expected in natural populations. Answering this question is important to evaluate the functional significance of adult neurogenesis under natural conditions and to define the factors controlling it. To address this issue, we investigated four species of wild-living rodents and outbred laboratory mice using markers for proliferating cells, Ki-67, and developing neurons, doublecortin and NeuroD. We found about four times as many Ki-67-positive cells per mm3 granule cell layer in two wood mouse species (Muridae; Apodemus spp.) than in bank and pine voles (Arvicolidae; Clethrionomys glareolus and Microtus subterraneus). Laboratory mice show proliferation rates between wood mice and voles. Markers for developing neurons, NeuroD and doublecortin, reflect the findings of proliferation activity. Hippocampal cell proliferation decreases dramatically with age in wild-living species. The onset of the downregulation varies among species. It occurs late in the life span of the yellow-necked wood mouse. In aged animals, the number of proliferating cells per mm3 granule cell layer is reduced to 19% of the adult value. Downregulation occurs early in pine voles, in which cell proliferation in adult animals is reduced to 33% of juvenile values. Proliferation and age-dependent changes along the deep border of the alveus and angular bundle follow those of the dentate gyrus. We conclude that cell proliferation and neurogenesis in the dentate gyrus vary significantly among wild-living rodents, and that they are downregulated with age, but at species-specific time points.

Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease

“…To extend and confirm the observations that neurally induced ADAS cells do not display characteristics of terminally differentiated neurons, we exposed ADAS cell cultures to a 4-day treatment of VPAsupplemented N2 serum-free medium, conditions previously reported to induce terminal differentiation of neural stem cells (Hsieh, Nakashima et al 2004). Consistent with results obtained after exposure to NDM, ADAS did not become terminally differentiated into mature neurons after exposure to N2/VPA as evidenced by persistent expression of the transcription factor NeuroD ( Figure 5, top panel) which is present in neuroblasts during the early stages of neural lineage commitment (Katayama, Mizuta et al 1997;Amrein, Slomianka et al 2004). Moreover, exposure to NDM induced outgrowth of processes in a subpopulation of the cells in the culture; yet these cells continued to express Ki67 ( Figure 5, white ovals) much like cells treated with the mitogenic cocktail EGF/FGF-2 in D10.…”

Adult neurogenesis is functionally associated with AD-like neurodegeneration

“…At LSND, however, these effects were dramatically decreased, indicating that the overall effect of the neurodegeneration on neurogenesis is decreased following neurodegenerative progression. As neurogenesis is down regulated by aging (Amrein, et al, 2004, Bondolfi, et al, 2004, Verret, et al, 2007, it is not clear whether this shift is or is not purely due to the effect of aging on neurogenesis. Second, the effect of neurodegeneration on neurogenesis is neurogenic stage-specific.…”

A morphologically distinct granule cell type in the dentate gyrus of the red fox correlates with adult hippocampal neurogenesis

“…For rodents, the time until a new born granule cells shows mature features is around 30 days (Brown et al, 2003;Kempermann et al, 2003), in contrast to possibly more than 3 months in monkeys (Ngwenya et al, 2006;Ngwenya et al, 2008). On the background of low proliferation, requirements for these highly excitable young neurons (Amrein et al, 2004b;Cameron and McKay, 2001;Deng et al, 2009) may be mediated by an extended maturation period.…”