CD36 deficiency affects depressive-like behaviors possibly by modifying gut microbiota and the inflammasome pathway in mice

Abstract

Both inflammatory processes and gut microbiota have been implicated in the pathophysiology of depressive disorders. The class B scavenger receptor CD36 is involved in the cytotoxicity associated with inflammation. However, its role in depression has not yet been examined. In this study, we investigated whether CD36 affects depression by modulating the microbiota-gut-inflammasome-brain axis. We used CD36−/− (knockout) mice subjected to chronic social defeat stress, and measured the expression of CD36 in these depressed mice and in patients with depression. The hippocampus of CD36−/− mice was used to investigate changes in the NLRP3 inflammasome signaling pathway. The 16S rRNA gene sequence-based approach was used to compare the cecal microbial communities in CD36−/− and WT mice. The CD36 deficiency in CD36−/− mice alleviated chronic stress-induced depression-like behaviors. CD36 was upregulated in depressed mice as well as in depressed patients. Furthermore, the NLRP3 inflammasome signaling pathway was downregulated in the hippocampus of CD36−/− mice. The Simpson Diversity Index revealed increased cecal bacterial alpha-diversity in the CD36−/− mice. Among genera, Bacteroides, Rikenella, and Alloprevotella were significantly more abundant in the CD36−/− mice, whereas Allobaculum was less abundant, consistent with the attenuated inflammation in the hippocampus of CD36−/− mice. Our findings suggest that CD36 deficiency changes the gut microbiota composition, which in turn may impact depressive-like behaviors by affecting the inflammasome pathway.

Lactobacillus paracasei CCFM1229 and Lactobacillus rhamnosus CCFM1228 Alleviated Depression- and Anxiety-Related Symptoms of Chronic Stress-Induced Depression in Mice by Regulating Xanthine Oxidase Activity in the Brain

“…CD36 deficiency may affect depressive-like behaviour by changing the intestinal microbiota and inflammasome pathways. Hippocampal CD36 mRNA expression was upregulated in the depressed mice, consistent with literature reports [ 13 ], whereas CCFM1228 significantly downregulated CD36 mRNA expression ( Figure 4 F).…”

Impact of Inosine on Chronic Unpredictable Mild Stress-Induced Depressive and Anxiety-Like Behaviors With the Alteration of Gut Microbiota

“…Each mouse was placed in the center with its nose facing an open quadrant, and the times spent in open and closed quadrants were measured for 5 min. After each mouse finished the OFT and the EPM, the floor surfaces and walls were scrubbed with 75% alcohol to abolish any olfactory cues ( Bai et al., 2021 ).…”

Gut Microbiota-Related Inflammation Factors as a Potential Biomarker for Diagnosing Major Depressive Disorder

“…The taxonomy of each OTU was analyzed by Ribosomal Database Project (RDP) Classifier algorithm (http:// rdp.cme.msu.edu/). The data of gut microbiota at OTU level in both groups was extracted from our previous study (Bai et al, 2021a).…”