BRAIN-DERIVED NEUROTROPHIC FACTOR PROMOTES THE SURVIVAL OF NEURONS ARISING FROM THE ADULT-RAT FOREBRAIN SUBEPENDYMAL ZONE

BRAIN-DERIVED NEUROTROPHIC FACTOR PROMOTES THE SURVIVAL OF NEURONS ARISING FROM THE ADULT-RAT FOREBRAIN SUBEPENDYMAL ZONE
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DOI:
10.1073/pnas.92.1.210
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发表时间:
1995-01-03
影响因子:
11.1
通讯作者:
GOLDMAN, SA
GOLDMAN, SA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
KIRSCHENBAUM, B;GOLDMAN, SA

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神经元前体细胞持续存在于成年前脑室管膜/室管膜下区(SZ),并已被发现产生来自鸟类,啮齿动物和人类的培养物中的神经元。我们推测,从这些细胞产生的神经元的生存可能会受到限制,在成年期的局部缺乏营养支持。为了验证这一假设,我们建立了成年大鼠前脑SZ的外植体培养,并评估了定义的神经营养因子对这些外植体产生的新神经元的存活的影响。我们发现,微管相关蛋白2(+)神经元来自广泛区域的SZ,跨越脑室系统的喙部6毫米的外植体。在暴露于脑源性神经营养因子(BDNF)的培养物中,>35%的新神经元在体外(DIV)22天时存活,并且>25%在42 DIV时存活,同时在未补充的对照中几乎完全丧失神经元。存活的细胞表达trkB,BDNF的高亲和力受体。相反,神经生长因子和神经营养因子3都不能提高神经元的存活率。因此,BDhF支持由成年大鼠前脑产生的神经元的存活,并且可以作为成年期神经元募集的容许因子。
Neuronal precursor cells persist in the adult forebrain ependymal/subependymal zone (SZ) and have been found to produce neurons in cultures derived from birds, rodents, and humans. We postulated that the survival of neurons generated from these cells might be constrained in adulthood by the local absence of trophic support. To test this hypothesis, we established explant cultures of adult rat forebrain SZ and assessed the effect of defined neurotrophins on the survival of new neurons arising from these explants. We found that microtubule-associated protein 2(+) neurons arose from explants derived from a wide area of the SZ, spanning the rostral 6 mm of the ventricular system. In cultures exposed to brain-derived neurotrophic factor (BDNF), >35% of new neurons survived at 22 days in vitro (DIV), and >25% survived at 42 DIV, concurrent with the virtually complete loss of neurons in unsupplemented controls. The surviving cells expressed trkB, the high-affinity receptor for BDNF. In contrast, neither nerve growth factor nor neurotrophic factor 3 enhanced neuronal survival. Thus, BDhF supports the survival of neurons produced by the adult rat forebrain and may act as a permissive factor for neuronal recruitment in adulthood.