Abstract
BackgroundEnvironmental enrichment (EE) is known to enhance BDNF levels and neurogenesis in the adult hippocampus. To examine the role of BDNF in modulating EE-mediated adult hippocampal neurogenesis, we conditionally ablated BDNF expression in the hippocampus (cKO mice) and have assessed proliferation, survival, differentiation and dendritic development of hippocampal progenitors.ResultsWe show that while the extent of cell proliferation and neuronal fate differentiation in the hippocampus of cKO mice is not different from wild-type (WT) littermates maintained in either standard or enriched conditions, reduced BDNF levels significantly impaired the survival of newborn cells in both housing conditions. In addition, while highly active enriched WT mice exhibited a robust increase in progenitor cell proliferation, highly active cKO mice showed a modest increase in cell proliferation compared to standard housed or underactive cKO mice.ConclusionsThere results argue that while BDNF plays a role in exercise-induced cell proliferation, other factors must contribute to this phenomenon. We also show that dendritic development was impaired in cKO mice maintained in standard housing conditions, and that EE rescued this phenotype.
Highlights
Environmental enrichment (EE) is known to enhance Brain-derived neurotrophic factor (BDNF) levels and neurogenesis in the adult hippocampus
To examine the influence of BDNF on maintaining basal levels of neurogenesis and/or EE-mediated neurogenesis, we examined mice in which BDNF expression was conditionally eliminated in mature neurons of the adult hippocampus
Analysis of BDNF levels in hippocampus of WT and cKO mice We previously demonstrated that conditional ablation of floxed PSEN1, encoding presenilin 1, by a CamKII-driven Cre transgene is initiated postnatally, and results in complete loss of PSEN1 expression in mature neurons in the hippocampal formation by the age of 3 months [16]
Summary
Environmental enrichment (EE) is known to enhance BDNF levels and neurogenesis in the adult hippocampus. To examine the role of BDNF in modulating EE-mediated adult hippocampal neurogenesis, we conditionally ablated BDNF expression in the hippocampus (cKO mice) and have assessed proliferation, survival, differentiation and dendritic development of hippocampal progenitors. Studies have shown that heterozygous BDNF knockout (BDNF+/) mice exhibit reduced [4] or enhanced cell proliferation [5] in the DG. The interpretation of these latter series of studies is confounded by the fact that BDNF+/mice exhibit a multiplicity of growth, metabolic, neuronal maturation and behavioral abnormalities [7,8,9,10] and it is very plausible that these phenotypes could have a significant influence on adult neurogenesis
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