Abstract
IntroductionAccumulating 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.MethodsmGluR5−/− 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.ResultsmGluR5−/− 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.ConclusionIn 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.
Highlights
Accumulating evidence indicates that the glutamatergic system plays an important role in the development of depression
All experimental mice were housed in groups in a room with controllable temperature and humidity and a 12/12-h light/ dark cycle. metabotropic glutamate receptor 5 (mGluR5)−/− mice were divided into three groups, group one (n = 7) for the open field (OF) and forced swim test (FST), group two (n = 7) for elevated plus maze EPM and TST, and group three (n = 8) for gut microbiota, protein, and inflammatory factor analysis
Our results suggest that mGluR5−/− mice had no significant despair-like or antidepressant behavior in the absence of stress exposure
Summary
Accumulating evidence indicates that the glutamatergic system plays an important role in the development of depression. Group I mGluRs are distributed primarily at postsynaptic excitatory synapses and are related to many neuropsychiatric diseases, such as anxiety, stress disorders, neurodegeneration, and depression [3, 5, 8]. It is noticeable, that the antidepressant-like effect of mGluR5 modulation is still controversial. Some studies showed that the antagonists of mGluR5 can effectively alleviate depression-like behaviors in rodents [9] and that the basal immobility of mGluR5−/− mice decreased in the forced swim test (FST) [9] and tail suspension test (TST) [1]. Shin et al.'s study showed that in many stress-induced models of depression, mGluR5−/− mice exhibited increased depression-like behaviors which could be reversed by rescue of mGluR5 in the shell of the nucleus accumbens (NAc) [10]
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