小胶质细胞
内分泌学
内科学
5-羟色胺能
前额叶皮质
单胺类
血清素
单胺类神经递质
野生型
清醒
化学
心理学
生物
神经科学
炎症
受体
医学
生物化学
基因
认知
突变体
脑电图
作者
Mohammed E. Choudhury,Kanta Mikami,Yuiko Nakanishi,Taisei Matsuura,Ryo Utsunomiya,Hajime Yano,Madoka Kubo,Rina Ando,Jun Iwanami,Masakatsu Yamashita,Masahiro Nagai,Junya Tanaka
标识
DOI:10.1016/j.jneuroim.2021.577794
摘要
Myeloid differentiation primary response gene 88 (MyD88) is essential for microglial activation. Despite the significant role of microglia in regulating sleep homeostasis, the contribution of MyD88 to sleep is yet to be determined. To address this, we performed electroencephalographic and electromyographic recordings on MyD88-KO mice and wild-type mice to investigate their sleep/wake cycles. In the daytime, MyD88-KO mice exhibited prolonged wakefulness and shorter non-rapid eye movement sleep duration. Tail suspension and sucrose preference tests revealed that MyD88-KO mice displayed a depressive-like phenotype. We determined monoamines in the prefrontal cortex (PFC) using high-performance liquid chromatography and observed a decreased content of serotonin in the PFC of MyD88-KO mice. Flow cytometry revealed that CD11b, CD45, and F4/80 expressions were elevated at Zeitgeber time (ZT) 1 compared to at ZT13 only in wild-type mice. Furthermore, MFG-E8 and C1qB-tagged synapses were enhanced at ZT1 in the PFC of wild-type mice but not in MyD88-KO mice. Primary cultured microglia from MyD88-KO mice revealed decreased phagocytic ability. These findings indicate that genetic deletion of MyD88 induces insomnia and depressive behavior, at least in part, by affecting microglial homeostasis functions and lowering the serotonergic neuronal output.
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