The Role for GABAergic Interneurons Subtypes in the Antidepressant Efficacy of Traditional Chinese Medicine Formula Lily Bulb and Rehmannia Decoction

Background Depression is associated with reduced γ-aminobutyric acid (GABA) and alterations of GABAergic interneurons in medial prefrontal cortex (mPFC), which can be normalized by traditional Chinese medicine formula lily bulb and Rehmannia decoction (LBRD) standard decoction. However, the impact of GABAergic interneurons subtypes including parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP), in depressive episodes as well as in the LBRD standard decoction antidepressant effects remains to be elucidated. Methods We assessed the effects of LBRD standard decoction intervention on the expression of GABA associated miRNA/mRNA and GABAergic subtype-specific markers in chronic stress induced depression by western blot and qRT-PCR. The lncRNA/miRNA/GABA regulatory axis was verified by luciferase reporter assay, RNA immunoprecipitation, RNA pull-down assay and then detect its changes in LBRD standard decoction administration with use of immunofluorescence staining and RNA-fluorescence in situ hybridization (FISH). Results In the current study, we found that LBRD standard decoction exerted antidepressant effects based on the results of behavioral tests. Meanwhile, LBRD also revised the reduced GABA levels in depression by increasing the expression of lncRNA Neat1 and Malat1, as well as decreasing miRNA-144-3p and miRNA-15b-5p. Moreover, the expression of SST mRNA and protein in the mPFC tissues from depression group, was significantly lower than those in the control cases, while LBRD standard decoction treatment revised these changes. Whereas, neither chronic stress nor treatment can obviously change the level of PV and VIP mRNA and protein expression. In the SST-positive neurons of mPFC tissues, treatment with LBRD standard decoction resulted in the elevation of Gad-67, VGAT, GAT-3 and an reduction of miRNA-144-3p expression. Conclusion Taken together, these findings suggest that SST interneurons may be served as a preferentially vulnerable GABAergic neuronal subtype in depression and LBRD standard decoction antidepressant activities potentially relate to against the SST cells deficits by regulating the miRNA-144-3p mediated GABA synthesis, release.