Amisulpride alleviates chronic mild stress-induced cognitive deficits: Role of prefrontal cortex microglia and Wnt/β-catenin pathway
Mohamed, Ahmed M; Habib, Mohamed Z.; Ebeid, Mai A; Abdelraouf, Sahar M; El Faramawy, Yasser; Aboul-Fotouh, Sawsan; Magdy, Yosra;
Abstract
Accumulating evidence indicates the role of microglial activation and sustained neuroinflammation in the pathogenesis of cognitive dysfunction, a common feature associated with depressive disorders. It also indicates the role of Wnt/β-catenin pathway in regulation of microglia-mediated neuroinflammation. Amisulpride exhibits antidepressant and pro-cognitive activities in several clinical and experimental studies. Hitherto, the direct effects of amisulpride on Wnt/β-catenin signaling and microglial activity have not been thoroughly studied. This study aimed at investigating the effects of chronic amisulpride treatment on Wnt/β-catenin signaling and pro-inflammatory microglial activation and its role in alleviation of depressive-like behavior and cognitive deficits elicited by unpredictable chronic mild stress (UCMS). The effects of amisulpride (3 mg/kg/day) were investigated on behavioral/cognitive deficits, expression of Wnt/β-catenin pathway and microglial activation in the prefrontal cortex (PFC) of UCMS-exposed male Wistar rats. UCMS induced depressive-like behavior with impairment of performance in novel object recognition test and attentional set-shifting task. These behavioral deficits were associated with decreased total β-catenin and increased pro-inflammatory microglial activation. Amisulpride improved UCMS-induced behavioral/cognitive deficits, ameliorated Wnt/β-catenin signaling dysregulation and pro-inflammatory microglial activation. This work highlights the antidepressant and pro-cognitive effects of amisulpride in UCMS-exposed rats that could be mediated by modulation of Wnt/β-catenin pathway activity and amelioration of pro-inflammatory microglial activation in the prefrontal cortex. This could provide new insights into the putative mechanisms behind the antidepressant and pro-cognitive effects exerted by amisulpride.
Other data
Title | Amisulpride alleviates chronic mild stress-induced cognitive deficits: Role of prefrontal cortex microglia and Wnt/β-catenin pathway | Authors | Mohamed, Ahmed M; Habib, Mohamed Z. ; Ebeid, Mai A; Abdelraouf, Sahar M; El Faramawy, Yasser; Aboul-Fotouh, Sawsan ; Magdy, Yosra | Keywords | Amisulpride;Cognitive dysfunction;Depression;Microglia;Neuroinflammation;Wnt/β catenin pathway | Issue Date | 15-Oct-2020 | Journal | European journal of pharmacology | Volume | 885 | ISSN | 00142999 | DOI | 10.1016/j.ejphar.2020.173411 | PubMed ID | 32800810 | Scopus ID | 2-s2.0-85089920801 |
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