Effects of lithium on cytokine neuro-inflammatory mediators, Wnt/β-catenin signaling and microglial activation in the hippocampus of chronic mild stress-exposed rats

• Published in: Toxicology and applied pharmacology Vol. 399; p. 115073
• Main Authors: Habib, Mohamed Z., Ebeid, Mai A., el Faramawy, Yasser, Saad, Sherin S.T., El Magdoub, Hekmat M., Attia, Azza A., Aboul-Fotouh, Sawsan, Abdel-Tawab, Ahmed M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-07-2020
• Subjects: Beta catenin; Chronic mild stress; Depression; Lithium; Microglia; Wnt signaling pathway; Depression; Chronic mild stress; Lithium; Wnt signaling pathway; Beta catenin; Microglia
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2020.115073

Microglial in vivo production of pro-inflammatory cytokines is central to the pathogenesis of multiple neurological disorders including depression, with a rising role of Wnt/β-catenin signaling as potential regulator of microglia-mediated neuro-inflammation. This study aimed at investigating the hippocampal expression of the Wnt/ß-catenin pathway in chronic mild stress (CMS)-exposed rats and the effects of Lithium (Li) on the expression of this pathway as a method to identify a plausible link between exposure to chronic stress, microglial activation, and neuroinflammation.
The effect of chronic administration of Li was investigated on behavioral changes, hippocampal expression of Wnt-DVL-GSK3β-β-catenin signaling pathway, and microglial activation in CMS-exposed male Wistar rats
CMS induced a depressive-like behavior associated with increased pro-inflammatory microglial activation and reduced hippocampal expression of the Wnt/β-catenin signaling pathway. Chronic Li treatment ameliorated stress induced-behavioral changes, reduced microglial activation and enhanced the hippocampal expression of Wnt/β-catenin signaling pathway.
This work highlights that Li-induced inhibition of GSK-3β with subsequent accumulation of β-catenin could impede pro-inflammatory microglia activation which is a key pathological hallmark associated with depression. Wnt/β-catenin signaling represents a promising therapeutic target, not only for alleviation of depression, but also for a wide array of neurological disorders.
•CMS exposure exaggerates pro-inflammatory microglial activation•Wnt/β-catenin signaling is involved in regulating stress induced neuro-inflammation•Chronic Li treatment alleviates CMS-induced pro-inflammatory microglial activation•Chronic Li treatment ameliorates CMS-induced dysregulated Wnt/β-catenin signaling