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[脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子(GDNF)中枢给药对具有抑郁样行为遗传易感性小鼠中5-羟色胺5-HT2A受体功能活性及表达的影响]

[The effect of central administration of the neurotrophic factors BDNF and GDNF on the functional activity and expression of the serotonin 5-HT2A receptors in mice genetically predisposed to depressive-like behavior].

作者信息

Tsybko A S, Il'chibaeva T V, Kondaurova E M, Bazovkina D V, Naumenko V S

出版信息

Mol Biol (Mosk). 2014 Nov-Dec;48(6):983-9.

Abstract

Brain serotonin (5-HT) system plays an important role in the control of normal and pathological behavior. 5-HT2A receptors are widely implicated in the regulation both normal functions and psychopathologies, especially schizophrenia and depression. Here, we investigated implication of 5-HT2A receptor in mechanisms of neurotrophic factors BDNF and GDNF action. We found that the acute intracerebroventricular injection of BDNF produced considerable increase in 5-HT2A receptor functional activity in ASC mice. Moreover, BDNF injection led to the increasing of 5-HT2A receptor gene expression in the hippocampus and its decrease in the frontal cortex without any effects in the midbrain. On the contrary, GDNF injection failed to alter 5-HT2A receptor functional activity, but increased the 5-HT2A receptor gene expression in the frontal cortex without any effects in the hippocampus and midbrain. Thus, an effect of the central administration of the neurotrophic factors BDNF and GDNF on the 5-HT2A receptor functional activity and gene expression was shown. The results indicate the implication of 5-HT2A receptor in the mechanisms of BDNF and GDNF action.

摘要

脑血清素(5-羟色胺,5-HT)系统在正常和病理行为的控制中发挥着重要作用。5-HT2A受体广泛参与正常功能和精神病理学的调节,尤其是精神分裂症和抑郁症。在此,我们研究了5-HT2A受体在神经营养因子脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子(GDNF)作用机制中的作用。我们发现,向ASC小鼠脑室内急性注射BDNF可使5-HT2A受体功能活性显著增加。此外,注射BDNF导致海马体中5-HT2A受体基因表达增加,额叶皮质中5-HT2A受体基因表达减少,而中脑无任何变化。相反,注射GDNF未能改变5-HT2A受体功能活性,但增加了额叶皮质中5-HT2A受体基因表达,而海马体和中脑无任何变化。因此,显示了神经营养因子BDNF和GDNF中枢给药对5-HT2A受体功能活性和基因表达的影响。结果表明5-HT2A受体参与了BDNF和GDNF的作用机制。

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