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C3aR in the medial prefrontal cortex modulates the susceptibility to LPS-induced depressive-like behaviors through glutamatergic neuronal excitability.
Sun, Rui; Tang, Meng-Yu; Yang, Dan; Zhang, Yan-Yi; Xu, Yi-Heng; Qiao, Yong; Yu, Bin; Cao, Shu-Xia; Wang, Hao; Huang, Hui-Qian; Zhang, Hong; Li, Xiao-Ming; Lian, Hong.
Afiliación
  • Sun R; Department of Neurology and Department of Psychiatry of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Research Center of System Medicine, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China; Biosensor National Special L
  • Tang MY; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
  • Yang D; Clinical Research Center, The second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Zhang YY; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
  • Xu YH; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
  • Qiao Y; Department of Neurology and Department of Psychiatry of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Research Center of System Medicine, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China.
  • Yu B; Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, China.
  • Cao SX; Department of Neurology, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Wang H; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Huang HQ; Clinical Research Center, The second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Zhang H; Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • Li XM; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
  • Lian H; Department of Neurology and Department of Psychiatry of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Research Center of System Medicine, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Novel Targ
Prog Neurobiol ; 236: 102614, 2024 May.
Article en En | MEDLINE | ID: mdl-38641040
ABSTRACT
Complement activation and prefrontal cortical dysfunction both contribute to the pathogenesis of major depressive disorder (MDD), but their interplay in MDD is unclear. We here studied the role of complement C3a receptor (C3aR) in the medial prefrontal cortex (mPFC) and its influence on depressive-like behaviors induced by systematic lipopolysaccharides (LPS) administration. C3aR knockout (KO) or intra-mPFC C3aR antagonism confers resilience, whereas C3aR expression in mPFC neurons makes KO mice susceptible to LPS-induced depressive-like behaviors. Importantly, the excitation and inhibition of mPFC neurons have opposing effects on depressive-like behaviors, aligning with increased and decreased excitability by C3aR deletion and activation in cortical neurons. In particular, inhibiting mPFC glutamatergic (mPFCGlu) neurons, the main neuronal subpopulation expresses C3aR, induces depressive-like behaviors in saline-treated WT and KO mice, but not in LPS-treated KO mice. Compared to hypoexcitable mPFCGlu neurons in LPS-treated WT mice, C3aR-null mPFCGlu neurons display hyperexcitability upon LPS treatment, and enhanced excitation of mPFCGlu neurons is anti-depressant, suggesting a protective role of C3aR deficiency in these circumstances. In conclusion, C3aR modulates susceptibility to LPS-induced depressive-like behaviors through mPFCGlu neuronal excitability. This study identifies C3aR as a pivotal intersection of complement activation, mPFC dysfunction, and depression and a promising therapeutic target for MDD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lipopolisacáridos / Corteza Prefrontal / Ratones Noqueados / Depresión / Neuronas Límite: Animals Idioma: En Revista: Prog Neurobiol Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lipopolisacáridos / Corteza Prefrontal / Ratones Noqueados / Depresión / Neuronas Límite: Animals Idioma: En Revista: Prog Neurobiol Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido