Henry Rebecca A, Hughes Stephanie M, Connor Bronwen
Department of Pharmacology and Clinical Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Eur J Neurosci. 2007 Jun;25(12):3513-25. doi: 10.1111/j.1460-9568.2007.05625.x.
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.
脑源性神经营养因子（BDNF）在调节成体脑内祖细胞的存活和命运方面发挥着重要作用。为了扩展先前在正常成体脑中的观察结果，并增进我们对BDNF对损伤脑内神经发生影响的了解，本研究直接比较了BDNF对基础和损伤诱导的神经发生的影响，涉及祖细胞分布以及神经元分化和存活水平。通过重组腺相关病毒（AAV(1/2)）递送，使BDNF在脑室下区（SVZ）过表达，并使用溴脱氧尿苷（BrdU）标记来鉴定新生成的细胞。在注射AAV(1/2) 21天后，通过单侧纹状体注射喹啉酸（QA）在一组大鼠中诱导选择性纹状体细胞丢失。在正常脑中，BDNF过表达显著增加了吻侧迁移流中BrdU阳性细胞的数量，表明祖细胞迁移增强。QA损伤后，我们观察到SVZ中BrdU免疫反应性降低。BDNF过表达使QA损伤的SVZ中BrdU阳性细胞数量恢复到正常脑中观察到的水平。最显著的是，BDNF增强了祖细胞向QA损伤纹状体的募集，并促进了正常和QA损伤纹状体中的神经元分化。我们的研究结果表明，BDNF增强了正常或QA损伤脑的神经源性和非神经源性区域中祖细胞的募集、神经元分化和存活。因此，增强BDNF的表达可能是增加内源性祖细胞神经发生的可行策略。
