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

Shunjie Bai,Zhi Chen,Peng Xie,Wei Wang,Ting Wang,Xunzhong Qi,Jianjun Chen,Juan Li,Shuxiao Zhang,Ke Cheng

doi:10.1038/s41398-020-01130-8

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.

Highlights

Major depressive disorder (MDD) has its root in interactions between genetic and environmental risk factors, resulting in complex and multifactorial etiology
We found that CD36 was significantly increased in the hippocampus of CSDS-exposed mice compared with control mice (Fig. 1f)
Our findings show that CD36 deficiency ameliorates the stress response by modulating the interaction between the inflammasome and the gut microbiota

Summary

Introduction

Major depressive disorder (MDD) has its root in interactions between genetic and environmental risk factors, resulting in complex and multifactorial etiology. The last decade has witnessed a growing interest in the contribution of microbiota-gut-brain axis to psychiatric disorders[6,7,8]. The definitive molecular mechanisms underlying the microbiota-gut-brain axis remain elusive. Pro-inflammatory cytokines have been demonstrated to play a critical role in the induction of depressive symptomatology[5]. Caspase-1, an inflammatory factor, participates in the response of immune cells to both pathogen-derived and endogenous mediators through formation of the inflammasome. Caspase-1 has been demonstrated to play a role in inflammatory forms of cell death as well as protein cleavage and secretion[11]. In our previous study of caspase-1 knockout mice, we found that inhibition of the caspase-1

Methods

Results

Discussion

Conclusion