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

机译:集中施用神经营养因子BDNF和GDNF对基因易感性抑郁样行为的小鼠功能活性和5-HT2A血清素受体表达的影响

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摘要

The brain's 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 of normal brain functions and in the pathogenesis of mental disorders, especially schizophrenia and depression. In this work, we studied the involvement of 5-HT2A receptors in the action of the brain-derived neurotrophic factor (BDNF) and the glial cell line-derived neurotrophic factor (GDNF). It was found that an acute intracerebroventricular BDNF injection caused a considerable increase in the functional activity of 5-HT2A receptors in ASC mice genetically predisposed to depression-like behavior. Moreover, as a result of the administration of BDNF, the expression of the 5-HT2A receptor gene increased in the hippocampus, decreased in the frontal cortex, and did not change in the midbrain. In contrast, GDNF administration did not affect the functional activity of 5-HT2A receptors, but increased the expression of the 5-HT2A receptor gene in the frontal cortex, but not in the hippocampus or the midbrain. Thus, the central administration of BDNF and GDNF was shown to affect the functional activity of 5-HT2A receptors and the expression of their genes. These results indicate that 5-HT2A receptors can be involved in the mechanisms of BDNF and GDNF action.
机译:大脑的5-羟色胺(5-HT)系统在控制正常和病理行为中起重要作用。 5-HT 2A受体广泛参与正常脑功能的调节以及精神障碍,尤其是精神分裂症和抑郁症的发病机理。在这项工作中,我们研究了5-HT2A受体参与脑源性神经营养因子(BDNF)和胶质细胞系源性神经营养因子(GDNF)的作用。已经发现,急性脑室内BDNF注射导致ASC小鼠中5-HT2A受体的功能活性显着增加,而ASC小鼠在基因上倾向于抑郁样行为。此外,由于施用BDNF,5-HT 2A受体基因的表达在海马中增加,在额叶皮质中减少,并且在中脑中没有改变。相比之下,GDNF给药并不影响5-HT2A受体的功能活性,但增加了5-HT2A受体基因在额叶皮层中的表达,但在海马或中脑中没有表达。因此,显示BDNF和GDNF的中央施用影响5-HT 2A受体的功能活性及其基因的表达。这些结果表明5-HT 2A受体可以参与BDNF和GDNF作用的机制。

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