Splenic nerve denervation attenuates depression-like behaviors in Chrna7 knock-out mice via the spleen-gut-brain axis.

BACKGROUND

Growing evidence highlights the role of the spleen-brain axis in inflammation-associated depression. The α7-subtype of nicotinic acetylcholine receptor (α7 nAChR, encoded by the Chrna7 gene) is implicated in systemic inflammation, with Chrna7 knock-out (KO) mice displaying depression-like behaviors. Yet, the influence of spleen nerve on depression-like behaviors in these KO mice remains to be elucidated.

METHODS

We investigated the effects of the splenic nerve denervation (SND) on depression-like behaviors, the protein expression in the prefrontal cortex (PFC), and the gut microbiota composition in Chrna7 KO mice.

RESULTS

SND markedly alleviated depression-like behaviors and the reduced expression of GluA1 and postsynaptic density protein-95 (PSD-95) in the PFC of Chrna7 KO mice. No changes in α-diversity of gut microbiota were noted among the control, KO + sham, and KO + SND groups. However, significant differences in β-diversity of gut microbiota were noted among the groups. Notable alterations in various microbiota (e.g., Fluviimonas_pallidilutea, Maribacter_arcticus, Parvibacter_caecicola) and plasma metabolites (e.g., helicide, N-acetyl-L-aspartic acid, α-D-galactose 1-phosphate, choline, creatine) were observed between KO + sham and KO + SND groups. Interestingly, correlations were found between the relative abundance of specific microbiota and other outcomes, including synaptic proteins, metabolites and behavioral data.

LIMITATIONS: The underlying mechanisms remain to be fully understood.

CONCLUSIONS

Our findings indicate that the splenic nerve contributes to depression-like phenotypes in Chrna7 KO mice via the spleen-gut-brain axis.