Prenatal stress differentially alters brain-derived neurotrophic factor expression and signaling across rat strains.
Prenatal stress differentially alters brain-derived neurotrophic factor expression and signaling across rat strains.
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DOI：
10.1016/j.neuroscience.2011.03.065
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发表时间：
2011-07-28
期刊：
影响因子：
3.3
通讯作者：
Leonard S
中科院分区：
文献类型：
--
作者：
Neeley EW;Berger R;Koenig JI;Leonard S
精神疾病和焦虑症有很强的神经发育成分。环境损伤，如产前暴露于压力和压力反应的遗传差异可能会影响大脑发育。采用随机变量产前应激大鼠模型，研究应激母鼠子代海马脑源性神经营养因子（BDNF）的表达和加工。为了解释未知的遗传影响，可能在这种产前应激范式的结果中发挥作用，研究了已知应激反应差异的三种不同大鼠品系：Fischer、Sprague-Dawley和刘易斯大鼠（n=132）。在三个菌株中发现BDNF的mRNA表达水平以及与其加工和信号传导相关的转录物的多重差异。在BDNF基因转录的众多剪接变体中，含有BDNF外显子VI的转录物在产前应激动物中最异常。未切割的proBDNF和成熟BDNF的蛋白水平也发生了改变，TrkB受体和Erk 1/2的磷酸化也改变了细胞内信号传导。变化不仅依赖于产前压力，但也应变依赖，表明遗传背景的重要性。BDNF信号既为神经元提供了积极的神经营养支持，也提供了消极的凋亡效应，这两者都可能有助于产前暴露于压力后的行为或神经化学结果。在三种大鼠品系中，产前应激后BDNF的差异处理对人类受试者具有影响，其中遗传差异可能保护或加剧胎儿发育期间环境应激源的影响。
Psychiatric illness and anxiety disorders have strong neurodevelopmental components. Environmental insults such as prenatal exposure to stress and genetic differences in stress responses may affect brain development. A rat model of random variable prenatal stress was used to study the expression and processing of hippocampal brain-derived neurotrophic factor (BDNF) in the offspring of the stressed rat dams. To account for unknown genetic influences that may play a role in the outcome of this prenatal stress paradigm, three different rat strains with known differences in stress responsivity were studied: Fischer, Sprague-Dawley, and Lewis rats (n=132). Multiple disparities in mRNA expression levels of BDNF, and transcripts related to its processing and signaling were found in the three strains. Of the numerous splice variants transcribed from the BDNF gene, the transcript containing BDNF exon VI was most aberrant in the prenatally stressed animals. Protein levels of both uncleaved proBDNF and mature BDNF were also altered, as was intra-cellular signaling by phosphorylation of the TrkB receptor and Erk 1/2. Changes were not only dependent on prenatal stress, but were also strain dependent, demonstrating the importance of genetic background. BDNF signaling provides both positive neurotrophic support for neurons and negative apoptotic effects, both of which may contribute to behavioral or neurochemical outcomes after prenatal exposure to stress. Differential processing of BDNF after prenatal stress in the three rat strains has implications for human subjects where genetic differences may protect or exacerbate the effects of an environmental stressor during fetal development.
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DOI：
10.1017/s1461145708008997
发表时间：
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影响因子：
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