Serotonergic neurotransmission mediated cognitive dysfunction in two mouse models of sepsis-associated encephalopathy.

Autor: Zhang C; Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China., Tian F; Department of Neurology, Xiangya Hospital, Central South University, Changsha, China., Peng J; Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China., Wang X; Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China., Li J; Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.; Bioinformatics Center & National Clinical Research Centre for Geriatric Disorders & Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Human, China., Zhang L; Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, China.; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.; Hunan Provincial Clinical Research Center for Critical Care Medicine, Changsha, Hunan, China., Tan Z; Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, China.; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.; Hunan Provincial Clinical Research Center for Critical Care Medicine, Changsha, Hunan, China.
Jazyk: angličtina
Zdroj: CNS neuroscience & therapeutics [CNS Neurosci Ther] 2024 Mar; Vol. 30 (3), pp. e14655.
DOI: 10.1111/cns.14655
Abstrakt: Background: Patients with sepsis-associated encephalopathy (SAE) often exhibit cognitive impairments. Despite this, the underlying mechanisms of SAE remain largely unexplored. Here, we explored the role of serotonergic neurotransmission in cognitive dysfunction of two mouse models of SAE.
Methods: The mouse models of SAE were established by injection of lipopolysaccharide (LPS, 10 mg/kg, intraperitoneal) and cecal ligation puncture (CLP) respectively. Barnes maze, new object recognition test and open field test were used to evaluate the effects of fluoxetine (selective serotonin reuptake inhibitor) and cyproheptadine (nonselective 5-HT 2 receptor antagonist) on cognition and motor activity of mice. Additionally, WAY100635 (5-HT 1A receptor antagonist) was co-administered with fluoxetine to explore the mechanism underlying effect of fluoxetine on cognitive impairments of SAE. Enzyme-linked immunosorbent assay (ELISA) was performed to determine 5-HT levels in hippocampus, brainstem and frontal lobe of experimental groups.
Results: Both LPS-induced sepsis and CLP induced sepsis resulted in a notable learning deficit. Fluoxetine ameliorated, while cyproheptadine aggravated, cognitive impairment in two classic mouse models of SAE. The cognition-enhancing effect of fluoxetine is reversed by WAY100635. Decreased 5-HT levels in hippocampus, brainstem and frontal lobe were observed in LPS septic model and CLP septic model. Notably, both fluoxetine and cyproheptadine significantly increased 5-HT levels in those brain regions in LPS septic model. Additionally, fluoxetine significantly increased 5-HT levels in frontal lobe of CLP septic model.
Conclusions: Our study demonstrated that serotonergic neurotransmission plays a significant role in mechanisms underlying cognitive impairment in SAE. These findings contribute to identification of novel targets to prevent and arrest cognitive impairment in SAE.
(© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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