Acute stimulation of vagus nerve modulates brain neurotrophins, and stimulates neuronal plasticity in the hippocampus of adult male rats

Pamela Rosso, M. Fiore, E. Fico, A. Iannitelli, P. Tirassa
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引用次数: 2

Abstract

The present study was aimed at evaluating whether single intermittent acute cervical vagus nerve stimulation (ACVS), pro-vided at a frequency which exhibits a clinical efficacy, may influence brain neurotrophins and hippocampal plasticity. With this purpose, the brain of adult male rats undergoing ACVS was used to analyze the expression of Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) in brain areas known to synthetize these growth factors, and the expression the neural cell adhesion molecule (NCAM), the synaptophysin (SYP) and biosynthetic GABA (GAD67) in the hippocampus. The effects of ACVS on NGF and BDNF protein and mRNA in hippocampus, hypothalamus and cortex two hours after stimulation were shown to be dependent on the frequencies of ACVS stimulation. Prolonged (three days post stimulation) modifications of NGF and BDNF were also observed in the hippocampus of ACVS rats. An early enhancement of the plasticity markers NCAM, SYP and GAD67 was also found in ACVS hippocampus. Three days after stimulation, NCAM and GAD67 levels were still higher than controls. Immunohistochemistry confirms the stimulatory effects of ACVS on GABA showing an increase in GAD67-positive cells in the dentate gyrus and CA3 hippocampal areas. This study shows that ACVS affects brain NGF and BDNF synthesis in a frequency-dependent manner. Neurotrophins changes are associated with increased hippocampal plasticity, as demonstrated by the observed molecular and morphological modifications. These findings support the role of brain neurotrophins in the ACVS mechanism of action.
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迷走神经急性刺激可调节脑营养因子,刺激成年雄性大鼠海马神经元可塑性
本研究旨在评估单次间歇性急性颈迷走神经刺激(ACVS)是否会影响脑神经营养因子和海马的可塑性。为此,我们利用ACVS成年雄性大鼠的大脑,分析神经生长因子(NGF)和脑源性神经营养因子(BDNF)在已知合成这些生长因子的脑区表达情况,以及海马区神经细胞粘附分子(NCAM)、突触素(SYP)和生物合成GABA (GAD67)的表达情况。刺激2小时后,ACVS对海马、下丘脑和皮层中NGF和BDNF蛋白及mRNA的影响与ACVS刺激频率有关。ACVS大鼠海马中也观察到长时间(刺激后3天)NGF和BDNF的改变。在ACVS海马中,可塑性标志物NCAM、SYP和GAD67也有早期增强。刺激3天后,NCAM和GAD67水平仍高于对照组。免疫组化证实了ACVS对GABA的刺激作用,显示齿状回和海马CA3区gad67阳性细胞增加。本研究表明,ACVS以频率依赖的方式影响脑NGF和BDNF的合成。神经营养物质的改变与海马可塑性的增加有关,正如观察到的分子和形态改变所证明的那样。这些发现支持了脑神经营养因子在ACVS作用机制中的作用。
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