Abstract
The functional role of adult neurogenesis in the hippocampus remains the subject of intense speculation. One recent hypothesis is that adult-born neurons contribute to the endocrine and behavioural outputs of the stress response. Here we show a genetic model system to ablate neurogenesis by inducibly deleting Tbr2 gene function specifically in the hippocampus and corroborate our findings in a radiation-based model of neurogenesis deprivation. We found that mice with ablation of new neurons in the dentate gyrus exhibit reduced anxiety during the dark cycle. After restraint stress, corticosterone levels in neurogenesis-deficient mice decreased more quickly than controls and were more sensitive to suppression by dexamethasone. Furthermore, glucocorticoid receptor target genes and neuronal activity markers showed reduced expression after stress in neurogenesis-deficient mice. These findings suggest that newborn neurons in the hippocampus are involved in sensing and eliciting an appropriate response to stress.
Highlights
The functional role of adult neurogenesis in the hippocampus remains the subject of intense speculation
A recent study using transgenic mice that express herpes virus thymidine kinase (TK) under the regulation of the mouse Glial Fibrillary Acidic Protein (GFAP) promoter revealed that neurogenesis could buffer neuroendocrine responses to stress[17]
T-box transcription factor highly expressed in neuronal progenitors in the hippocampus[18], and we have previously demonstrated that TBR2 is essential for adult neurogenesis[19]
Summary
The functional role of adult neurogenesis in the hippocampus remains the subject of intense speculation. Glucocorticoid receptor target genes and neuronal activity markers showed reduced expression after stress in neurogenesis-deficient mice. These findings suggest that newborn neurons in the hippocampus are involved in sensing and eliciting an appropriate response to stress. It has been reported that behavioural changes following treatment with antidepressants are lost in mice that have undergone hippocampal irradiation This irradiation decreased 85% of cell proliferation in the hippocampus, suggesting that neurogenesis is required for antidepressants to evoke behavioural changes[14]. This study shed some light on the complexity of neurogenesis and the stress response As these data were largely based on a single model, the GFAP-TK mouse, additional studies are needed to validate this conclusion. We revealed that mice without DG neurogenesis feature a reduced response to stress and less anxiety
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