利他林对幼年大鼠额叶皮层小清蛋白阳性中间神经元c-Fos表达的影响
本文选题:利他林 + 小清蛋白中间神经元 ; 参考:《生理学报》2017年04期
【摘要】:目前已知注意力缺损多动症(attention-deficit hyperactivity disorder,ADHD)的发病机制与额叶皮层活动降低、多巴胺(dopamine,DA)和去甲肾上腺素(norepinephrine,NE)不足有关。利他林目前是临床治疗ADHD的首选使用药物。它是单胺类递质转运体抑制剂,通过阻断转运体,提高细胞外DA和NE浓度,达到治疗效果。除此之外,利他林还可以增强皮层锥体神经元的兴奋性,增强皮层整体的活动。但是,利他林对中间神经元活动的影响尚不清楚。本研究采用药理学和免疫组织化学技术,探讨全身注射利他林对幼年大鼠眶额皮层(orbitofrontal cortex,OFC)、前额叶皮层(prefrontal cortex,PFC)和前扣带皮层(anterior cingulate cortex,ACC)中小清蛋白(parvalbumin,PV)阳性中间神经元c-Fos表达的影响。结果显示,利他林显著增加OFC的内侧区(MO)、腹侧区(VO)和外侧区(LO)c-Fos的表达,但是仅增加MO区和VO区PV阳性中间神经元c-Fos的表达,对LO区PV阳性中间神经元c-Fos表达没有影响;对PFC前边缘区(Pr L)和缘下回区(IL)的分析显示,只有剂量为1 mg/kg的利他林可使这两个区域c-Fos的表达和PV阳性中间神经元c-Fos的表达明显增多,而8 mg/kg的利他林则无显著作用。利他林可使ACC中c-Fos的表达和PV阳性中间神经元c-Fos的表达显著增多。以上结果表明,对幼年大鼠全身给予利他林,可以激活其额叶皮层PV阳性中间神经元,提示利他林可能通过激活皮层PV阳性神经元调控皮层锥体神经元动作电位的发放和神经元网络的同步活动,影响皮层的输出。
[Abstract]:The pathogenesis of attention deficit hyperactivity disorder (ADHD) is related to the decrease of frontal cortex activity, the deficiency of dopamine dopamine (DA) and norepinephrine (NE).Ritalin is currently the preferred drug for clinical treatment of ADHD.It is a monoamine transmitter transporter inhibitor. By blocking the transporter, the extracellular concentration of DA and NE is increased and the therapeutic effect is achieved.In addition, Ritalin can also enhance the excitability of cortical pyramidal neurons and enhance the overall activity of the cortex.However, the effect of Ritalin on intermediate neuron activity is unclear.In this study, pharmacological and immunohistochemical techniques were used to investigate the effects of systemic injection of Ritalin on the expression of c-Fos in the medial neurons of Orbitofrontal cortexus OFC, prefrontal Cortex prefrontal Cortex (PFCs) and anterior cingulate Cortex (ACCs) of parvalvalbumin PVV in juvenile rats.The results showed that Ritalin significantly increased the expression of LOC-Fos in the medial, ventral) and lateral regions of OFC, but only increased the expression of c-Fos in PV-positive interneurons in MO and VO regions, but had no effect on the c-Fos expression of PV-positive interneurons in Lo region.The analysis of PFC in the anterior marginal region (pr L) and the inferior marginal region (IL) showed that only 1 mg/kg of Ritalin could significantly increase the expression of c-Fos and the expression of c-Fos in PV-positive interneuron, but Ritalin at 8 mg/kg had no significant effect.Ritalin significantly increased the expression of c-Fos and PV positive interneuron c-Fos in ACC.These results suggest that the administration of Ritalin in the whole body of young rats can activate the PV-positive interneurons in the frontal cortex.It is suggested that Ritalin may affect cortical output by activating cortical PV positive neurons to regulate the release of action potential of cortical pyramidal neurons and the synchronous activity of neural networks.
【作者单位】: 复旦大学脑科学研究院;
【基金】:supported by the National Natural Science Foundation of China(No.31571098)
【分类号】:R749.94
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