Fig. 3: HFD downregulates glutamate transporters, GLAST and GLT-1, in the vHPC of mice and knockdown of the vHPC GLAST and GLT-1 reproduces HFD-related circuit and behavioral impairments in naïve mice. | Molecular Psychiatry

Fig. 3: HFD downregulates glutamate transporters, GLAST and GLT-1, in the vHPC of mice and knockdown of the vHPC GLAST and GLT-1 reproduces HFD-related circuit and behavioral impairments in naïve mice.

From: High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens

Fig. 3

Effects of a 12-week HFD on parameters of interests. a and b Measurements of expression of glutamatergic transmission-related molecules in the vHPC of mice. a Representative micrographs of Western blots. b Quantitative results. n = 10 mice per group. Measurements of expression of GABAergic transmission-related molecules in the vHPC of mice. c Representative micrographs of Western blots. d Quantitative results. n = 10 mice per group. Measurement of extracellular glutamate concentrations in the vHPC of mice. e Quantitative results. n = 10 mice per group. f Locations of biosensor tips in real-time measurement of extracellular level of glutamate. Blue dash line indicates the inserting track in the upper panel. S: subiculum; CA1: cornu ammonis 1; SNR: substantia nigra pars reticulata. g Experimental timelines of studies determining effects of lentiviral knockdown of vHPC GLAST and GLT-1 on activity of vHPC→NAc glutamatergic transmission and depression-like behaviors in naïve mice. h Efficacy of lentiviral knockdown of vHPC GLAST and GLT-1. Left panels show representative micrographs of Western blots. Right panel shows quantitative results. n = 8 mice in shLacZ group; n = 11 mice in shGLAST+shGLT-1 group. i Results of SPT. n = 4 cages of mice in shLacZ group; n = 5 cages of mice in shGLAST+shGLT-1 group. j Results of FST. n = 8 mice in shLacZ group; n = 11 mice in shGLAST+shGLT-1 group. Measurements of c-Fos expression in the FG-labeled vHPC→NAc glutamatergic neurons in naïve mice. k Representative fluorescence images of c-Fos-immunoreactive cells (green) and FG-labeled NAc-projecting cells (blue) in the vHPC. Scale bar, 100 µm. l Number of FG-labeled cells. m Percentage of FG-labeled cells also expressing c-Fos. n = 6 mice per group. All data are expressed as mean ± SD. n.s. not significant. See also Supplementary Tables S1 and S2 for details of animal usage and statistical test results.

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