Fig. 1: Lack of ACSS2 causes defects of synaptic formation and reduces levels of BDNF and TPH2 to induce depressive symptoms.

A Immobility time in the tail suspension test, forced swimming test, and sucrose consumption in the sucrose preference test from male mice in individual animals from wild type, Acss2^−/− and Acss2^+/− groups (n = 8–10). B Representative immunoblots and quantification of hippocampal ACSS2, BDNF, TPH2 protein levels normalized to loading controls (n = 4) from wild type, Acss2^−/− and Acss2^+/− male mice. C C57BL/6 J male mice were injected with lentivirus of ACSS2 or control group with NC (2μl was injected into the left and right hippocampus respectively; n =8–10 male mice per group) in stereotactic location in the hippocampus. TST, FST, and SPT behavioral tests were performed 4 weeks after the injection of lentivirus. D Immobility time in the tail suspension test, forced swimming test, and sucrose consumption in the sucrose preference test from male mice in individual animals from si-NC and si-ACSS2 groups (n =8–10). E Representative photomicrographs of dendritic spines from DG granular cells, scale bar, 10 μm. And Spine density in dendrites of DG granular cells, (si-NC n = 4 and siACSS2 n = 3 per group). Values are indicated as mean ± SD one-way ANOVA and multiple comparison test, *P ≤ 0.05 **P ≤ 0.01. All the experiments were repeated at least three times independently. F Analysis of BDNF content of HIP by ELISA in male mice from si-NC and si-ACSS2 groups (n = 7–9). G Representative immunoblots and quantification of hippocampal ACSS2, BDNF, TPH2 protein levels normalized to loading controls (n = 6) from si-ACSS2 male mice. H Analysis of 5-HT, DA and NA/NE content of HIP by ELISA in male mice from si-NC and si-ACSS2 groups (n = 6–9). I Immobility time in the tail suspension test from male mice in individual animals from control and CRS groups (n =9–10). J Representative photomicrographs of dendritic spines from DG granular cells, scale bar, 10 μm. K RT-PCR analysis of ACSS2 expression levels in Hip of male mice (n =6–8) exposure to Control and CRS. Data were normalized with GAPDH mRNA levels and presented as fold changes compared with control group. Scale bars represent mean values and error bars represent SEM. L Representative immunoblots and quantification of hippocampal ACSS2, BDNF, TPH2 protein levels normalized to loading controls (n = 4) from Control and CRS male mice. M Analysis of 5-HT content of HIP by ELISA in male mice from Control and CRS groups (n =5–6).