Analysis of the Gut Microbiota and Inflammatory Factors in mGluR5-Knockout Mice

Accumulating evidence indicates that the glutamatergic system plays an important role in the development of depression. Notably, the antidepressant effect of metabotropic glutamate receptor 5 (mGluR5) modulation is inconsistent across studies. Here, we attempted to identify the involvement of the gut microbiota and inflammation in mGluR5^-/- mice.

mGluR5^-/- mice and their wild-type littermates were used in our study. We used the open field (OF) and elevated plus maze (EPM) tests to assess anxiety-like behaviors, and we used the two-day forced swim test (FST) and tail suspension test (TST) to test despair-like behaviors. 16S rDNA was used to analyze the gut microbiota. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of inflammatory factors. Western blotting was used to detect the levels of various proteins.

mGluR5^-/- mice had no significant increase or decrease of despair-like behavior in the absence of stress exposure. However, mGluR5^-/- mice exhibited despair-like behaviors following stress exposure. No significant changes in other glutamate receptors or representative synaptic proteins were detected in the prefrontal cortex (PFC) or hippocampus of mGluR5^-/- mice. Very similar bacterial groups were observed in mGluR5^-/- mice and wild-type controls. In addition, there was no significant difference in the α-diversity of the microbiota between mGluR5^-/- mice and wild-type controls. The levels of all measured cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, and TNF-α) did not change significantly in the PFCs or colons of mGluR5^-/- mice.

In conclusion, we deduced that mGluR5^-/- mice are susceptible to despair-like behavior. The systemic knockout of mGluR5 did not affect the gut microbiota or inflammatory factors in mice.