本文選題：利他林 + 小清蛋白中間神經(jīng)元��； 參考：《生理學(xué)報(bào)》2017年04期

【摘要】：目前已知注意力缺損多動癥(attention-deficit hyperactivity disorder,ADHD)的發(fā)病機(jī)制與額葉皮層活動降低、多巴胺(dopamine,DA)和去甲腎上腺素(norepinephrine,NE)不足有關(guān)。利他林目前是臨床治療ADHD的首選使用藥物。它是單胺類遞質(zhì)轉(zhuǎn)運(yùn)體抑制劑,通過阻斷轉(zhuǎn)運(yùn)體,提高細(xì)胞外DA和NE濃度,達(dá)到治療效果。除此之外,利他林還可以增強(qiáng)皮層錐體神經(jīng)元的興奮性,增強(qiáng)皮層整體的活動。但是,利他林對中間神經(jīng)元活動的影響尚不清楚。本研究采用藥理學(xué)和免疫組織化學(xué)技術(shù),探討全身注射利他林對幼年大鼠眶額皮層(orbitofrontal cortex,OFC)、前額葉皮層(prefrontal cortex,PFC)和前扣帶皮層(anterior cingulate cortex,ACC)中小清蛋白(parvalbumin,PV)陽性中間神經(jīng)元c-Fos表達(dá)的影響。結(jié)果顯示,利他林顯著增加OFC的內(nèi)側(cè)區(qū)(MO)、腹側(cè)區(qū)(VO)和外側(cè)區(qū)(LO)c-Fos的表達(dá),但是僅增加MO區(qū)和VO區(qū)PV陽性中間神經(jīng)元c-Fos的表達(dá),對LO區(qū)PV陽性中間神經(jīng)元c-Fos表達(dá)沒有影響;對PFC前邊緣區(qū)(Pr L)和緣下回區(qū)(IL)的分析顯示,只有劑量為1 mg/kg的利他林可使這兩個區(qū)域c-Fos的表達(dá)和PV陽性中間神經(jīng)元c-Fos的表達(dá)明顯增多,而8 mg/kg的利他林則無顯著作用。利他林可使ACC中c-Fos的表達(dá)和PV陽性中間神經(jīng)元c-Fos的表達(dá)顯著增多。以上結(jié)果表明,對幼年大鼠全身給予利他林,可以激活其額葉皮層PV陽性中間神經(jīng)元,提示利他林可能通過激活皮層PV陽性神經(jīng)元調(diào)控皮層錐體神經(jīng)元動作電位的發(fā)放和神經(jīng)元網(wǎng)絡(luò)的同步活動,影響皮層的輸出。
[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.
【作者單位】： 復(fù)旦大學(xué)腦科學(xué)研究院;
【基金】：supported by the National Natural Science Foundation of China(No.31571098)
【分類號】：R749.94

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