Journal Article

5-HT attenuates chronic stress-induced cognitive impairment in mice through intestinal flora disruption

Wang, Ran, Wang, Zixu, Chen, Yaoxing, Ma, Junxing, Dong, Yulan

2023

Overview

Background The microbiota–gut–brain axis plays an important role in the development of depression. The aim of this study was to investigate the effects of 5-HT on cognitive function, learning and memory induced by chronic unforeseeable mild stress stimulation (CUMS) in female mice. CUMS mice and TPH2 KO mice were used in the study. Lactococcus lactis E001-B-8 fungus powder was orally administered to mice with CUMS. Methods We used the open field test, Morris water maze, tail suspension test and sucrose preference test to examine learning-related behaviours. In addition, AB-PAS staining, immunofluorescence, ELISA, qPCR, Western blotting and microbial sequencing were employed to address our hypotheses. Results The effect of CUMS was more obvious in female mice than in male mice. Compared with female CUMS mice, extracellular serotonin levels in TPH2 KO CUMS mice were significantly reduced, and cognitive dysfunction was aggravated. Increased hippocampal autophagy levels, decreased neurotransmitter levels, reduced oxidative stress damage, increased neuroinflammatory responses and disrupted gut flora were observed. Moreover, L. lactis E001-B-8 significantly improved the cognitive behaviour of mice. Conclusions These results strongly suggest that L. lactis E001-B-8 but not FLX can alleviate rodent depressive and anxiety-like behaviours in response to CUMS, which is associated with the improvement of 5-HT metabolism and modulation of the gut microbiome composition.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 5-HT / Animal cognition / Animals / Antidepressants / Anxiety / Autophagy / Behavior / Behavior, Animal / Biomedical and Life Sciences / Biomedicine / Care and treatment / Cognition / Cognition disorders / Cognitive ability / Cognitive Dysfunction - drug therapy / Cognitive Dysfunction - etiology / Cognitive Dysfunction - metabolism / Cognitive impairment / Composition / CUMS / Depression - drug therapy / Depression - etiology / Depression - metabolism / Diagnosis / Digestive system / Disease Models, Animal / Enzyme-linked immunosorbent assay / Female / Gastrointestinal Microbiome / Gastrointestinal tract / Gut microbiome / Gut-brain axis / Hippocampus / Hippocampus - metabolism / Homeostasis / Immunofluorescence / Immunology / Inflammation / Intestinal microflora / Laboratory animals / Learning / Male / Memory / Mice / Microbiomes / Microbiota / Microbiota (Symbiotic organisms) / Nervous system / Neurobiology / Neurology / Neurosciences / Open-field behavior / Oral administration / Oxidative stress / Prevention / Probiotics / Receptors / Risk factors / Serotonin / Serotonin - metabolism / Stress / Stress (Psychology) / Stress, Psychological - complications / Stress, Psychological - metabolism / Sucrose / The gut-brain axis: Emerging evidence in health and disease / Western blotting