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胰淀素作用于背外侧被盖核胆碱乙酰转移酶神经元调节小鼠体重OA北大核心CSTPCD

Amylin Acts on Choline Acetyltransferase Neurons in the Lateral Dorsal Tegmental Nucleus(LDT)to Regulate Body Weight of Mice

中文摘要英文摘要

胰淀素(amylin)作用于背外侧被盖核(lateral dorsal tegmental nucleus,LDT),诱导减肥和抑食效应,并激活背肩胛棕色脂肪组织(interscapular brown adipose tissue,IBAT)产热.多种食欲激素受体与胆碱乙酰转移酶(choline acetyltransferase,ChAT)神经元共同定位于LDT中,以调节饱腹感和能量消耗.然而,LDT的ChAT神经元是否参与胰淀素介导的体重调节作用尚待探索.作者拟通过免疫荧光检测小鼠LDT中原癌基因蛋白(c-Fos)和ChAT神经元的表达,逆行示踪技术确认LDT的下游神经核团,神经元损伤试验分析胰淀素作用的神经机制.结果显示:腹腔注射胰淀素显著降低小鼠体重,并显著促进LDT和臂旁核(PBN)中c-Fos和ChAT神经元表达.ChAT和神经型一氧化氮合成酶(nNOS)神经元在LDT、PBN和迷走神经背侧核(DMV)中共表达.逆行示踪试验证明LDT向PBN神经元发送神经投射.此外,损伤LDT和PBN神经元可降低胰淀素的减肥效果.LDT是连接PBN的能量平衡调节中枢,ChAT神经元参与介导胰淀素的体重调节过程.

Amylin acts on the lateral dorsal tegmental nucleus(LDT),induces weight loss and diet-suppressive effects,and activates dorsal scapular brown adipose tissue(IBAT)to produce heat.Multiple appetite hormone receptors colocalized with choline acetyltransferase(ChAT)neurons in LDT to modulate saturation and energy expenditure.However,it remains to be determined whether ChAT neurons in LDT are involved in amylin-mediated weight regulation.Immunofluorescence was conducted to detect the expression of c-Fos and ChAT neurons in mouse LDT,retrograde tracer analysis was selected to confirme the downstream nucleus mass of LDT,and neuronal damage assays was conducted to analyze the neuromechanism of amylin action.Results showed that intraperitoneal administration of amylin significantly reduced the body weight of mice and significantly increased the expression of c-Fos and ChAT neurons in both the LDT and parabrachial nucleus(PBN).ChAT and neuronal nitric oxide synthase(nNOS)neurons were co-expressed in the dorsal motor nucleus of the vagus(DMV).Retrograde tracer experiments demonstrated that LDTs send nerve projections to PBN neurons.Furthermore,injury of LDT and PBN neurons reduced the weight loss of amylin.LDT is the center of energy balance regulation connected to PBN,and the ChAT neurons of this circuit are involved in the process of weight regulation of amylin.

曹晓娟;陈玉洁;张小宇;海日汗;杜晨光;刘昊东;李鹏辉;李嘉成;樊奇;王星;李彩琴;杨子程;郭永清

内蒙古农业大学职业技术学院,包头 014109内蒙古农业大学职业技术学院,包头 014109||内蒙古自治区基础兽医学重点实验室,呼和浩特 010018||内蒙古农业大学兽医学院,呼和浩特 010018内蒙古自治区基础兽医学重点实验室,呼和浩特 010018||内蒙古农业大学兽医学院,呼和浩特 010018

畜牧业

肥胖胆碱乙酰转移酶胰淀素下丘脑背外侧被盖核

obesitycholine acetyltransferaseamylinhypothalamuslateral dorsal tegmental nucleus

《畜牧兽医学报》 2024 (007)

3185-3192 / 8

国家自然科学基金(32060204);内蒙古科技攻关计划(2021GG0199);内蒙古自然科学基金(2020MS03035);内蒙古自治区教育厅高等学校科学研究项目(NJZY22535);内蒙古自治区直属高校基本科研业务费项目(BR220150);内蒙古自治区高等学校科学研究重点项目(NJZZ22529);内蒙古自治区教育厅高等学校科学研究项目(NJZY23120)

10.11843/j.issn.0366-6964.2024.07.036

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