The Role of Notch1 in adult Hippocampal Neurogenesis and function

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Title: The Role of Notch1 in adult Hippocampal Neurogenesis and function
Author: Ables, Jessica Lynn
Abstract: Neurogenesis occurs throughout life in the hippocampal subgranular zone (SGZ ) and is potently stimulated by exercise , but the underlying mechanisms are still poorly defined . Notch1 is a master regulator of developmental neurogenesis , yet its role in adult hippocampal neurogenesis is unclear . To test the hypothesis that cell -intrinsic Notch1 is critical to both basal and exercise -induced SGZ neurogenesis , we generated Nestin -creERT2 /R26R -YFP /Notch1loxP /loxP (Notch1 iKO ) mice to inducibly ablate Notch1 in Nestin -expressing stem and progenitor SGZ cells . The total number of YFP+ SGZ cells increased over time in wild type littermates , but not in Notch1 iKO mice . Morphological and phenotypic analyses revealed that fewer YFP+ DG neurons were generated over time in Notch1 iKO mice due to smaller pools of YFP+ stem -like and progenitor cells . Likewise , neural progenitors isolated from Notch1 iKO mice were incapable of forming new neurospheres with extended passaging . While non -running Notch1 iKO mice had fewer YFP+ SGZ cells relative to wild type littermates , Notch1 iKO mice given 30 days access to a running wheel had equal number of YFP+ SGZ cells relative to controls , suggesting that running rescued total YFP+ SGZ cell number independent of Notch1 . However , running did not rescue YFP+ stem -like cell number in Notch1 iKO mice , suggesting that the putative stem -like SGZ cells make little contribution to adult hippocampal neurogenesis in these conditions . From these data , we conclude that Notch1 in Nestin+ stem and progenitor cells is critical to maintain basal adult hippocampal neurogenesis , but is not critical for exercise -induced neurogenesis . Neurogenesis has also been implicating in depression and behavioral response to antidepressants . To determine if reduced neurogenesis contributed to depression - or anxiety -related behavior , we assessed several measures of depression and anxiety in Notch1 iKO mice . We found that Notch1 iKO mice did not differ from WT mice in their behavior , suggesting that reduced neurogenesis is not associated with mood disturbances .
URI: http : / /hdl .handle .net /2152 .5 /223
Date: 2009-09-04


The Role of Notch1 in adult Hippocampal Neurogenesis and function. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /223 .

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