Fig. 4: GABAA-α5 within the MC4RdBNST neurons mediates HFD-induced mental dysfunction and obesity. | Molecular Psychiatry

Fig. 4: GABAA-α5 within the MC4RdBNST neurons mediates HFD-induced mental dysfunction and obesity.

From: Reciprocal control of obesity and anxiety–depressive disorder via a GABA and serotonin neural circuit

Fig. 4

a Expression level of major GABAAR-α5 subunits within the dBNST of WT mice treated with LFD or HFD Error bars represent mean ± SEM. n = 9 per group; *p < 0.05; two-way ANOVA and followed by Bonferroni comparisons test. b Diagram showing the trans-synaptic tracing by injection of AAV9-FLEX-WGA-ZsGreen into the ARC of AgrpCre mice. c–e Co-localization of the dBNST neurons directly innervated by AgRP neurons (c) and GABAAR-α5 (e). Inset in (e) is a magnified view of the boxed area showing colocalized neurons with arrow heads. Scale bar in (e) for (c–e), 150 μm; scale bar in the inset of (e), 30 μm. f–i OFT (f, g), and EPM test (h, i) by Mc4rCre::Rosa26Cas9 mice with bilateral injection of either vehicle (Vehicle), AAV9-FLEX-Gabra5sgRNA-tdTomato (Gabra5sgRNA) into the dBNST. Error bars represent mean ± SEM. n = 7–10 per group; *p < 0.05; one-way ANOVA and followed by Tukey comparisons test. j–o EPM (j, k), OFT (l), FST (m), TST (n), and MBT (o) test in CNO or vehicle-treated Mc4rCre mice with either AAV9-FLEX-hM4Di-mCherry or AAV9-FLEX-Gabra5cDNA-tdTomato into the dBNST followed with a chronic treatment of HFD or LFD. Error bars represent mean ± SEM. n = 8 per group; *p < 0.05, LFD + CNO vs HFD + hM4Di+Veh; #p > 0.05, LFD + CNO vs HFD + hM4Di+CNO; ‡p > 0.05, LFD + CNO vs HFD + Gabra5cDNA; one-way ANOVA and followed by Tukey comparisons test. p Body weight (left) and daily food intake (right) in LFD or HFD-treated Mc4rCre mice with injection of AAV9-FLEX-Gabra5cDNA-tdTomato into the dBNST. Error bars represent mean ± SEM. n = 9 per group; *p < 0.05, HFD vs HFD + Gabra5sgRNA; two-way ANOVA and followed by Bonferroni comparisons test. q Combined intake of HFD and LFD in a food preference test in mice as described in (J). Error bars represent mean ± SEM. n = 9 per group; *p < 0.05, LFD vs Gabra5cRNA and HFD vs Gabra5cRNA in the intake of LFD; #p < 0.05 LFD vs Gabra5cRNA and HFD vs Gabra5cRNA in the intake of HFD. Two-way ANOVA and followed by Bonferroni comparisons test. r Macronutrient composition of daily food intake by the mice as described in (p).

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