A 5-HT6R agonist alleviates cognitive dysfunction after traumatic brain injury in rats by increasing BDNF expression

• Published in: Behavioural brain research 2022-09, Vol.433, p.113997-113997, Article 113997
• Main Authors: Ou, Fu-Yong, Ning, Ya-Lei, Yang, Nan, Chen, Xing, Peng, Yan, Zhao, Yan, Li, Ping, Zhou, Yuan-Guo, Liu, Yan
• Format: Article
• Language: English
• Subjects: 5-HT6 receptors; Brain-derived neurotrophic factor; Cognition; Traumatic brain injury
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2022.113997

Effective treatment for cognitive dysfunction after traumatic brain injury (TBI) is lacking in clinical practice. Increased brain-derived neurotrophic factor (BDNF) expression in cognitive circuits can significantly alleviate cognitive dysfunction in animal models of TBI. Selective 5-hydroxytryptamine receptor 6 (5-HT6R) agonists significantly increase BDNF expression and improve cognitive function. Therefore, we evaluated the protective effect of a highly selective 5-HT6R agonist, WAY-181187, on cognitive dysfunction after TBI. We established a controlled cortical impact model of moderate TBI in rats and performed drug intervention for five consecutive days. Rats had spatial reference memory impairment in the Morris water maze one and four weeks after TBI. BDNF expression in the medial prefrontal cortex (mPFC) and hippocampus decreased two and five weeks after TBI. Additionally, five weeks after TBI, decreases in neuronal dendritic spine density and the proportion of thin, mushroom-shaped dendritic spines and an increased proportion of stubby-type dendritic spines were observed. WAY-181187 administration (3 mg/kg) for five consecutive days after TBI significantly alleviated cognitive dysfunction at one and four weeks (P