小胶质细胞在光/暗周期过程中调节海马突触传递和睡眠持续时间  

Microglia modulate hippocampal synaptic transmission and sleep duration along the light/dark cycle

作　　者：杜一星(编译) Giorgio Corsi;Katherine Picard;Maria Amalia di Castro;Stefano Garofalo;Federico Tucci;Giuseppina Chece;Claudio Del Percio;Maria Teresa Golia;Marcello Raspa;Ferdinando Scavizzi;Fanny Decoeur;Clotilde Lauro;Mara Rigamonti;Fabio Iannello;Davide Antonio Ragozzino;Eleonora Russo;Giovanni Bernardini;Agnès Nadjar;Marie Eve Tremblay;Claudio Babiloni;Laura Maggi;Cristina Limatola(Department of Physiology and Pharmacology,Sapienza University of Rome,Rome,Italy;Axe Neurosciences,Centre de Recherche du CHU de Québec,UniversitéLaval,Quebec City,Quebec,Canada;Department of Neurology,San Raffaele of Cassino,Cassino(FR),Italy;National Research Council,Institute of Biochemistry and Cell Biology(EMMA/Infrafrontier/IMPC),International Campus"A.Buzzati-Traverso",Rome,Italy;INRAE,Bordeaux INP,NutriNeuro UMR 1286,Bordeaux University,Bordeaux,France;Tecniplast S.P.A.,Buguggiate,Varese,Italy;Department of Molecular Medicine,Sapienza University,Rome,Italy;INSERM,Neurocentre Magendie,Physiopathologie de la PlasticitéNeuronale,Bordeaux,France;Division of Medical Sciences,University of Victoria,Victoria,British Columbia,Canada;The Department of Biochemistry and Molecular Biology,The University of British Columbia,Vancouver,British Columbia,Canada;Department of Physiology and Pharmacology,Sapienza University,Laboratory affiliated to Istituto Pasteur Italia,Rome,Italy;Department of Neurophysiology,Neuropharmacology,Inflammaging,IRCCS Neuromed,Pozzilli,Italy)

机构地区：[1]不详

出　　处：《神经损伤与功能重建》2022年第5期310-310,共1页Neural Injury and Functional Reconstruction

摘　　要：小胶质细胞是大脑的常驻巨噬细胞,通过感知神经元活动并支持突触重塑和可塑性积极促进脑实质的稳态。虽然已有研究表明星形胶质细胞在睡眠中的不同作用,但小胶质细胞在调节睡眠/觉醒周期和白天不同阶段调节突触活动中的作用尚未深入研究。以光作为授时提示,我们研究了用集落刺激因子-1受体拮抗剂PLX5622消除小胶质细胞对雄性小鼠睡眠/觉醒周期和海马突触传递的影响。我们的数据表明,小胶质细胞几乎完全的耗竭会增加NREM睡眠的持续时间并减少海马兴奋性神经传递。由于cx3cr1GFP/GFP小鼠显现与PLX5622处理的小鼠中发现的相同情况,趋化因子fractalkine受体CX3CR1在这些效应中起相关作用。此外,在光照阶段小胶质细胞表达较低水平的cx3cr1;当培养的小胶质细胞受到ATP(一种在睡眠期间释放的嘌呤能分子)的刺激时其cx3cr1表达降低。我们的研究结果表明,小胶质细胞参与调节睡眠,调整其cx3cr1表达以响应光/暗阶段,并以时相依赖性方式调节突触活动。Microglia,the brain's resident macrophages,actively contribute to the homeostasis of cerebral parenchyma by sensing neuronal activity and supporting synaptic remodeling and plasticity.While several studies demonstrated different roles for astrocytes in sleep,the contribution of microglia in the regulation of sleep/wake cycle and in the modulation of synaptic activity in the different day phases has not been deeply investigated.Using light as a zeitgeber cue,we studied the effects of microglial depletion with the colony stimulating factor-1 receptor antagonist PLX5622 on the sleep/wake cycle and on hippocampal synaptic transmission in male mice.Our data demonstrate that almost complete microglial depletion increases the duration of NREM sleep and reduces the hippocampal excitatory neurotransmission.The fractalkine receptor CX3CR1 plays a relevant role in these effects,because cx3cr1GFP/GFP mice recapitulate what found in PLX5622-treated mice.Furthermore,during the light phase,microglia express lower levels of cx3cr1 and a reduction of cx3cr1 expression is also observed when cultured microglial cells are stimulated by ATP,a purinergic molecule released during sleep.Our findings suggest that microglia participate in the regulation of sleep,adapting their cx3cr1 expression in response to the light/dark phase,and modulating synaptic activity in a phase-dependent manner.

关 键 词：CX3CR1 脑电图 长期增强 小胶质细胞耗竭 微型兴奋性突触后电流 睡觉 眠 自发兴奋性突触后电流 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]