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AAV‐mediated delivery of BDNF augments neurogenesis in the normal and quinolinic acid‐lesioned adult rat brain
Author(s) -
Henry Rebecca A.,
Hughes Stephanie M.,
Connor Bronwen
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05625.x
Subject(s) - neurogenesis , quinolinic acid , progenitor cell , subventricular zone , neurotrophic factors , brain derived neurotrophic factor , striatum , neuroscience , rostral migratory stream , biology , neural stem cell , stem cell , microbiology and biotechnology , dopamine , tryptophan , biochemistry , receptor , amino acid
Brain‐derived neurotrophic factor (BDNF) plays a major role in regulating the survival and fate of progenitor cells in the adult brain. In order to extend previous observations in the normal adult brain and advance our knowledge regarding the effect of BDNF on neurogenesis in the injured brain, this study directly compared the effect of BDNF on basal and injury‐induced neurogenesis in relation to progenitor cell distribution and levels of neuronal differentiation and survival. BDNF was overexpressed in the subventricular zone (SVZ) via recombinant adeno‐associated virus (AAV 1/2 ) delivery, and newly generated cells were identified using bromodeoxyuridine (BrdU) labelling. Selective striatal cell loss was induced in a subgroup of rats by unilateral striatal injection of quinolinic acid (QA) 21 days after AAV 1/2 injection. In the normal brain, BDNF overexpression significantly increased BrdU‐positive cell numbers in the rostral migratory stream, indicating enhanced progenitor cell migration. Following QA lesioning, we observed a reduction in BrdU immunoreactivity in the SVZ. Overexpression of BDNF restored BrdU‐positive cell numbers in the QA‐lesioned SVZ to that observed in the normal brain. Most significantly, BDNF enhanced the recruitment of progenitor cells to the QA‐lesioned striatum and promoted neuronal differentiation in both the normal and QA‐lesioned striatum. Our findings indicate that BDNF augments the recruitment, neuronal differentiation and survival of progenitor cells in both neurogenic and non‐neurogenic regions of the normal or QA‐lesioned brain. Enhanced expression of BDNF may therefore be a viable strategy for augmenting neurogenesis from endogenous progenitor cells.