Activation of early neural progenitors is required for traumatic brain injury-induced hippocampal neurogenes

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Title: Activation of early neural progenitors is required for traumatic brain injury-induced hippocampal neurogenes
Author: Yu, Tzong-Shiue
Abstract: Traumatic brain injury (TBI ) is the most common form of acquired brain injury in both children and adults in the United States . TBI causes neuronal loss and results in a variety of neurological impairments and deficits in hippocampus -dependent functions . However , cognitive recovery commonly occurs though the mechanism is unknown . Exploration of post -natal neurogenesis in the hippocampus raises the possibility that adult -born neurons may contribute to cognitive recovery from TBI . Several studies in animal models that mimic TBI demonstrate there is enhanced generation of adult -born neurons in the dentate gyrus and those adult -born neurons may correlate with cognitive recovery . Due to the limits of current methodology in studying neurogenesis , it remains unclear what relevance injury -induced neurogenesis may have in the recovery process following TBI . In order to explore the relevance of injury -induced neurogenesis , I have characterized a previously generated transgenic mouse line that has rtTA -IRES -eGFP expression under the control of a nestin promoter and also contains a neural progenitor -specific regulatory element . By using this line , I have demonstrated that eGFP -expressing cells represent early neural progenitors in the adult dentate gyrus . Performing unilateral controlled cortical injury (CCI ) demonstrates that this injury depletes doublecoritn (Dcx ) -expressing late neural progenitors while activating eGFP -expressing early neural progenitors . To address whether the subsequent recovery of Dcx -expressing late progenitors was derived from activation of early neural progenitors , I generated a transgenic line that expresses modified herpes simplex viral thymidine kinase (delta -HSV -TK ) under the control of the neural progenitor -specific regulatory element of the nestin gene . This allows for temporally regulated ablation of dividing neural progenitors by exposing the animal to ganciclovir . Using this line , I demonstrate that ablation of dividing GFP -expressing early neural progenitors in neurogenic areas occurs only in the presence of ganciclovir . CCI on these mice , reveals that no newly born Dcx -expressing late neural progenitors are observed seven days after injury when exposed to ganciclovir . However , the repopulation of Dcx -expressing cells is apparent when ganciclovir was removed one day before injury . Four weeks after injury , those newly born Dcx -expressing cells became mature NeuN -expressing neurons . This suggests that injury -induced activation of early neural progenitors is required for the recovery of injured hippocampal neurons .
URI: http : / /hdl .handle .net /2152 .5 /324
Date: 2008-09-19

Citation

Activation of early neural progenitors is required for traumatic brain injury-induced hippocampal neurogenes. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /324 .

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