Optogenetic Stimulation of mPFC Alleviates White Matter Injury-Related Cognitive Decline after Chronic Ischemia through Adaptive Myelination.
Optogenetic Stimulation of mPFC Alleviates White Matter Injury-Related Cognitive Decline after Chronic Ischemia through Adaptive Myelination.
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DOI：
10.1002/advs.202202976
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发表时间：
2023-02
期刊：
影响因子：
15.1
通讯作者：
Xu, Yun
中科院分区：
文献类型：
--
作者：
Deng, Shiji;Shu, Shu;Zhai, Lili;Xia, Shengnan;Cao, Xiang;Li, Huiya;Bao, Xinyu;Liu, Pinyi;Xu, Yun
反映髓磷脂损失的白色物质损伤（White Matter Injury，白质损伤）有助于由脑血管疾病引起的认知下降或痴呆。然而，由于缺乏专门用于药物治疗的药物，因此需要探索新的治疗策略。最近发现，适应性髓鞘形成是大脑功能的稳态控制所必需的。在这项研究中，适应性髓鞘形成相关策略被应用于探索缺血性脑血管病相关认知功能障碍的治疗。在这里，双侧颈动脉狭窄（BCAS）被用来模拟缺血性脑血管病相关的认知障碍，并揭示内侧前额叶皮层（mPFC）中神经元的光遗传学和化学遗传学激活促进胼胝体中少突胶质细胞前体细胞（OPC）的分化，从而改善髓鞘修复和工作记忆。从机制上讲，这些神经调节技术通过诱导Wnt 2从活化的神经元轴突分泌来发挥治疗作用，其作用于少突胶质细胞前体细胞并驱动少突胶质细胞发生和髓鞘形成。因此，这项研究表明，神经调节是一个有前途的战略，指导髓鞘修复和认知功能的恢复，通过适应性髓鞘形成的背景下，缺血性脑血管病。慢性缺血后mPFC神经元的光遗传和化学发生激活上调神经元衍生的Wnt 2的表达，Wnt 2作用于OPCs并促进其向少突胶质细胞分化，导致髓鞘修复和认知功能改善。目前的发现强调了神经调节是在慢性缺血的背景下指导适应性髓鞘形成的一种有前途的策略。
White matter injury (WMI), which reflects myelin loss, contributes to cognitive decline or dementia caused by cerebral vascular diseases. However, because pharmacological agents specifically for WMI are lacking, novel therapeutic strategies need to be explored. It is recently found that adaptive myelination is required for homeostatic control of brain functions. In this study, adaptive myelination‐related strategies are applied to explore the treatment for ischemic WMI‐related cognitive dysfunction. Here, bilateral carotid artery stenosis (BCAS) is used to model ischemic WMI‐related cognitive impairment and uncover that optogenetic and chemogenetic activation of glutamatergic neurons in the medial prefrontal cortex (mPFC) promote the differentiation of oligodendrocyte precursor cells (OPCs) in the corpus callosum, leading to improvements in myelin repair and working memory. Mechanistically, these neuromodulatory techniques exert a therapeutic effect by inducing the secretion of Wnt2 from activated neuronal axons, which acts on oligodendrocyte precursor cells and drives oligodendrogenesis and myelination. Thus, this study suggests that neuromodulation is a promising strategy for directing myelin repair and cognitive recovery through adaptive myelination in the context of ischemic WMI. Optogenetic and chemogenetic activation of mPFC glutamatergic neurons after chronic ischemia upregulate the expression of neuron‐derived Wnt2, which acts on OPCs and promotes their differentiation toward oligodendrocytes, leading to myelin repair and improved cognitive function. The current finding highlights that neuromodulation is a promising strategy for directing adaptive myelination in the context of chronic ischemia.
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影响因子：
25
作者：
Hughes EG;Orthmann-Murphy JL;Langseth AJ;Bergles DE
通讯作者：
Bergles DE
DOI：
10.1523/jneurosci.3467-12.2013
发表时间：
2013-02-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lang J;Maeda Y;Bannerman P;Xu J;Horiuchi M;Pleasure D;Guo F
通讯作者：
Guo F
影响因子：
16.2
作者：
Canoll, PD;Musacchio, JM;Salzer, JL
通讯作者：
Salzer, JL
影响因子：
3.5
作者：
Feigenson, Keith;Reid, Mary;Grinspan, Judith B.
通讯作者：
Grinspan, Judith B.
Wnt/β-连环蛋白信号传导对少突胶质细胞发育的阶段特异性调节
影响因子：
5.3
作者：
Dai, Zhong-Min;Sun, Shuhui;Qiu, Mengsheng
通讯作者：
Qiu, Mengsheng