短暂性脱髓鞘导致长期认知障碍、髓鞘改变和神经网络同步缺陷  

Transient demyelination causes long-term cognitive impairment,myelin alteration and network synchrony defects

作　　者：Océane Mercier Pascale P Quilichini Karine Magalon Florian Gil Antoine Ghestem Fabrice Richard Thomas Boudier Myriam Cayre Pascale Durbec 杜一星(编译) 

机构地区：[1]UMR7288 after IBDM,Aix Marseille Univ,CNRS,IBDM,Marseille,France [2]U1106 after INS,Aix Marseille Univ,INSERM,INS,Inst Neurosci Syst,Marseille,France [3]Aix Marseille Univ,Turing Centre for Living Systems,Marseille,France [4]不详

出　　处：《神经损伤与功能重建》2024年第3期F0003-F0003,共1页Neural Injury and Functional Reconstruction

摘　　要：在成年大脑中,活动依赖性髓鞘可塑性是正确学习和记忆巩固所必需的。因此,髓鞘的丢失、改变,甚至细微的结构变更都会损害神经网络活动,导致功能障碍。在多发性硬化症中,虽然自发的髓鞘修复过程是可能的,但患者之间存在异质性。髓鞘修复有时会导致功能恢复,这通常在运动水平比在认知水平更明显。在铜宗处理的小鼠模型中,大量脑脱髓鞘随后发生自发且强烈的髓鞘再生。然而,重组髓鞘虽然具有功能,但可能不会表现出与发育髓鞘相同的形态特征,这可能会对神经网络的活动产生影响。基于此,本研究使用铜腙处理的小鼠模型来分析短暂性脱髓鞘对脑结构、功能和认知的长期影响。本研究结果表明,尽管脱鞘事件后存在髓鞘再生,但仍会导致长期认知障碍,例如空间工作记忆、社交记忆、认知灵活性和多动症的缺陷。这些缺陷与内侧前额叶皮质(m PFC)和海马体(HPC)髓鞘含量的减少以及结构髓鞘修饰有关,表明这些结构中的髓鞘再生过程可能不完善。在体电生理记录表明,脱髓鞘事件改变了HPC-mPFC活动的同步性,这对于记忆过程至关重要。总而言之,本研究数据表明,短暂脱髓鞘后的髓鞘修复过程不允许完全恢复皮质结构中的初始髓鞘特性。这些细微的变更改变了神经网络特征并导致小鼠长期认知缺陷。In the adult brain,activity-dependent myelin plasticity is required for proper learning and memory consoli-dation.Myelin loss,alteration,or even subtle structural modifications can therefore compromise the network activity,leading to functional impairment.In multiple sclerosis,spontaneous myelin repair process is possible,but it is hetero-geneous among patients,sometimes leading to functional recovery,often more visible at the motor level than at the cognitive level.In cuprizone-treated mouse model,massive brain demyelination is followed by spontaneous and ro-bust remyelination.However,reformed myelin,although functional,may not exhibit the same morphological charac-teristics as developmental myelin,which can have an impact on the activity of neural networks.In this context,we used the cuprizone-treated mouse model to analyze the structural,functional,and cognitive long-term effects of tran-sient demyelination.Our results show that an episode of demyelination induces despite remyelination long-term cogni-tive impairment,such as deficits in spatial working memory,social memory,cognitive flexibility,and hyperactivity.These deficits were associated with a reduction in myelin content in the medial prefrontal cortex(mPFC)and hippo-campus(HPC),as well as structural myelin modifications,suggesting that the remyelination process may be imperfect in these structures.In vivo electrophysiological recordings showed that the demyelination episode altered the synchro-nization of HPC-mPFC activity,which is crucial for memory processes.Altogether,our data indicate that the myelin repair process following transient demyelination does not allow the complete recovery of the initial myelin properties in cortical structures.These subtle modifications alter network features,leading to prolonged cognitive deficits in mice.

关 键 词：认知 多发性硬化症小鼠模型 髓鞘再生 神经网络活动 

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]