Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity
Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity
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DOI：
10.1196/annals.1403.009
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Marini, Ann M.
中科院分区：
文献类型：
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作者：
Lipsky, Robert H.;Marini, Ann M.
神经营养因子对哺乳动物中枢神经系统的发育和维持至关重要。其中包括脑源性神经营养因子(BDNF)，它的合成和释放是通过激活谷氨酸受体来实现的。这一过程的扰动可能是神经退行性疾病和精神疾病的基础。人类的一种自然发生的变异，以66密码子多肽(Val66->；Met)前区域常见的单核苷酸多态的形式，影响前BDNF多肽的加工及其激活依赖的释放。这种变异与海马区结构体积的差异以及焦虑和抑郁相关的表型有关。在一只人源化的BDNF转基因小鼠身上发现了支持BDNF在改变海马体结构和行为中的作用的趋同发现。此外，最近的人类遗传学研究通过编码BDNF同源受体的TrkB基因的等位基因、基因型和单倍型与酒精依赖之间的关联，支持BDNF信号在成瘾行为中的作用。更好地了解BDNF介导的通路在细胞存活和可塑性中的影响，将有助于开发新的方法来恢复疾病状态下的正常功能。
Neurotrophins are critical to the development and maintenance of the mammalian central nervous system. Among them is brain-derived neurotrophic factor (BDNF), whose synthesis and release is targeted by activation of glutamate receptors. Perturbation of this process probably underlies neurodegenerative and psychiatric disorders. A naturally occurring variation in humans, in the form of a common single-nucleotide polymorphism in the pro region of the polypeptide at codon 66 (Val66 -> Met), affects processing of the pro-BDNF polypeptide and its activation-dependent release. This variant is associated with differences in the volume of the hippocampal formation and with anxiety and depression-related phenotypes. Convergent findings supporting a role for BDNF in alterations to hippocampal structure and behavior are found in a "humanized" BDNF transgenic mouse. Also, recent human genetic studies have supported a role of BDNF signaling in addictive behaviors by allele-, genotype-, and haplotype-based association of the TrkB gene, which encodes the cognate receptor for BDNF, with alcohol dependence. A better understanding of the influence of BDNF-mediated pathways in cell survival and plasticity will aid in developing new approaches to restoring normal function in disease states.