CD33/TREM2 Signaling Mediates Sleep Deprivation-Induced Memory Impairment by Regulating Microglial Phagocytosis
CD33/TREM2 Signaling Mediates Sleep Deprivation-Induced Memory Impairment by Regulating Microglial Phagocytosis
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CD33/TREM2 信号通过调节小胶质细胞吞噬作用介导睡眠剥夺引起的记忆损伤
DOI：
10.1007/s12017-023-08733-6
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发表时间：
2023-01
影响因子：
3.5
通讯作者：
Zhai Qian
中科院分区：
文献类型：
--
作者：
Tan Shuwen;Gao Hui;Sun Jianyu;Li Na;Zhang Yuxin;Yang Liu;Wang Min;Wang Qiang;Zhai Qian
睡眠剥夺会导致健康成年人的记忆力明显受损。广泛的研究集中在确定记忆障碍的生物学机制。小胶质细胞介导的突触消除在睡眠剥夺中起着不可或缺的作用。在此，评估了CD 33/TREM 2信号通路在慢性睡眠限制（CSR）期间调节记忆衰退中的潜在作用。在这项研究中，使用自动睡眠剥夺仪对成年雄性C57 BL/6小鼠进行睡眠限制，每天20小时，持续7天。Y-迷宫测试显示，与对照组小鼠相比，CSR小鼠的自发交替显著减少。与对照小鼠相比，CSR小鼠对新物体的探索偏好百分比显着降低。这些记忆缺陷与异常的小胶质细胞活化和吞噬能力增加有关。此外，在CSR小鼠中，海马组织中的CD 33蛋白水平显著下调，但TREM 2蛋白水平升高。在BV 2小胶质细胞中，下调CD 33增加了TREM 2表达并改善了小胶质细胞的吞噬作用。然后，将唾液酸配体单唾液酸神经节苷脂1（GM 1，20 mg/kg，i. p.）在CSR期间每天一次给予小鼠。我们的研究结果进一步表明，GM 1激活CD 33，从而干扰TREM 2介导的小胶质细胞吞噬作用。最后，GM 1通过海马CA 1区的CD 33/TREM 2信号通路逆转CSR诱导的突触丢失和记忆障碍。这项研究提供了新的证据，表明激活CD 33和/或抑制TREM 2活性代表了通过调节小胶质细胞吞噬作用治疗睡眠丧失诱导的记忆缺陷的潜在疗法。
Sleep deprivation causes significant memory impairment in healthy adults. Extensive research has focused on identifying the biological mechanisms underlying memory impairment. Microglia-mediated synaptic elimination plays an indispensable role in sleep deprivation. Here, the potential role of the CD33/TREM2 signaling pathway in modulating memory decline during chronic sleep restriction (CSR) was evaluated. In this study, adult male C57BL/6 mice were sleep-restricted using an automated sleep deprivation apparatus for 20 h per day for 7 days. The Y-maze test revealed that spontaneous alternation was significantly reduced in CSR mice compared with control mice. The percentage of exploratory preference for the novel object in CSR mice was significantly decreased compared with that in control mice. These memory deficits correlated with aberrant microglial activation and increased phagocytic ability. Moreover, in CSR mice, the CD33 protein level in hippocampal tissue was significantly downregulated, but the TREM2 protein level was increased. In BV2 microglial cells, downregulation of CD33 increased TREM2 expression and improved microglial phagocytosis. Then, the sialic ligand monosialo-ganglioside 1 (GM1, 20 mg/kg, i.p.) was administered to mice once a day during CSR. Our results further showed that GM1 activated CD33 and consequently disturbed TREM2-mediated microglial phagocytosis. Finally, GM1 reversed CSR-induced synaptic loss and memory impairment via the CD33/TREM2 signaling pathway in the CA1 region of the hippocampus. This study provides novel evidence that activating CD33 and/or inhibiting TREM2 activity represent potential therapies for sleep loss-induced memory deficits through the modulation of microglial phagocytosis.
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影响因子：
7.8
作者：
Natalia Yanguas-Casás;Andrea Crespo-Castrillo;M. Arevalo;L. Garcia-Segura
通讯作者：
Natalia Yanguas-Casás;Andrea Crespo-Castrillo;M. Arevalo;L. Garcia-Segura
影响因子：
9.3
作者：
Wadhwa M;Prabhakar A;Ray K;Roy K;Kumari P;Jha PK;Kishore K;Kumar S;Panjwani U
通讯作者：
Panjwani U
影响因子：
15.1
作者：
Rangaraju S;Dammer EB;Raza SA;Rathakrishnan P;Xiao H;Gao T;Duong DM;Pennington MW;Lah JJ;Seyfried NT;Levey AI
通讯作者：
Levey AI
影响因子：
5.9
作者：
Bhattacherjee, Abhishek;Rodrigues, Emily;Macauley, Matthew S.
通讯作者：
Macauley, Matthew S.
影响因子：
10.6
作者：
Karch CM;Goate AM
通讯作者：
Goate AM