Project description:Microdissected ventromedial hypothalamus (VMH) was profiled to identify transcriptional changes after Nkx2-1 ablation in female mice. Total RNA was extracted from conditional mutants (Nkx2-1 f/f; Sf1Cre) and floxed controls (Nkx2-1 f/f) at postnatal day 10 (P10) and profiled using Mouse ref8 v2.0 Illumina chips and reagents (n=4/group). The tissue profiled is microdissected ventromedial hypothalamus from P10 female mice. Controls and mutants are analyzed in quadruplicate.
Project description:To uncover the cellular architecture of the mouse ventromedial hypothalamus (VMH), we used single nucleus RNA-seq (snRNA-seq) from wild-type mice.
Project description:To uncover the cellular architecture of the macaque ventromedial (VMH) and dorsomedial hypothalamus (DMH), we used single nucleus RNA-seq (snRNA-seq) from a Rhesus macaque
Project description:The paraventricular hypothalamus (PVH) is crucial for food intake control, yet the presynaptic mechanisms underlying PVH neurons remain unclear. Here, we show that RUVBL2 in the PVH is significantly reduced during energy deficit, and knockout (KO) of PVH RUVBL2 results in hyperphagic obesity in mice. RUVBL2-expressing neurons in the PVH (PVHRUVBL2) exert the anorexigenic effect by projecting to the arcuate hypothalamus, the dorsomedial hypothalamus, and the parabrachial complex. We further demonstrate that PVHRUVBL2 neurons form the synaptic connections with POMC and AgRP neurons in the ARC. PVH RUVBL2 KO impairs the excitatory synaptic transmission by reducing presynaptic boutons and synaptic vesicles near active zone. Finally, RUVBL2 overexpression in the PVH suppresses food intake and protects against diet induced obesity. Together, this study demonstrates an essential role for PVH RUVBL2 in food intake control, and suggests that modulation of synaptic plasticity could be an effective way to curb appetite and obesity.
Project description:Analysis of gene expression in the paraventricular nucleus in the hypothalamus (PVH) of WT and Sim1-Cre specific DNMT3a deletion mice. Results provide important information about genes regulated by DNMT3a.
Project description:The purpose of this study was to identify miRNA that are differentially regulated in the arcuate nucleus of the hypothaamus (ARC) and paraventricular nucleus of the hypothalamus (PVH) after perinatal exposure to maternal obesity.
Project description:Analysis of gene expression regulated by FoxO1 in the ventromedial hypothalamus (VMH) of wildtype and knockout mice. Results provide important information of gene expression in the VMH. The transcription factor FoxO1 contributes to leptin and insulin action, including cells in the brain. However, the neurons mediating these effects and the identity of the molecular targets through which FoxO1 exerts metabolic actions remains to be defined.
Project description:Analysis of gene expression regulated by FoxO1 in the ventromedial hypothalamus (VMH) of wildtype and knockout mice. Results provide important information of gene expression in the VMH. The transcription factor FoxO1 contributes to leptin and insulin action, including cells in the brain. However, the neurons mediating these effects and the identity of the molecular targets through which FoxO1 exerts metabolic actions remains to be defined. For the gene expression profiling, total RNA was obtained from the VMH of WT and VMH-specific FoxO1 KO mice using Qiagen RNeasy Lipid Tissue Mini Kit (Qiagen Sciences, Maryland) and Phase Lock Gel (5 Prime Inc., Gaithersburg, MD). To make sure reproducibility and biological significance, triple hybridizations were performed for each genotype with the RNA from three independent VMH samples, each sample contains RNA from three animals (biological replicates). Genomics and Microarray Core Facility at UT-Southwestern (http://microarray.swmed.edu/) checked RNA quality with Bioanalyzer Chip and processed the samples for hybridization with Illumina Mouse-6 V2 BeadChip (Illumina Inc., San Diego, CA). We used Partek Genomics Suite 6.5 (Partek Inc., St Louis, MO) and Ingenuity Pathway Analysis (Ingenuity Systems, Inc., Redwood City, CA) for data analysis.
Project description:The ventromedial nucleus of the hypothalamus (VMH) is thought to a satiety center and a potential target for anti-obesity therapy. Electroconvulsive seizure (ECS) therapy is highly effective in psychiatric diseases including depression, but also implicated beneficial effects on other neurological diseases. Although it has been reported that the neurons in the VMH are strongly activated by ECS stimulation, the effect of ECS in this hypothalamic subnucleus remains unknown. To address this issue, we investigated molecular changes in the VMH in response to ECS by utilizing a method of laser-capture microdissection coupled with microarray analysis, and examined behavioral effects of ECS via VMH activation. ECS significantly induced gene expression not only immediate-early genes such as Fos, Fosb and Jun, but also Bdnf, Adcyap1, and Hrh1 in the VMH after a single or repeated stimulus. Mice received one or 7 times shock of ECS and their brains were collected at 2 h (VMH_1stECS2h, VMH_7thECS2h) or 6 h after shock (VMH_1stECS6h, VMH_7thECS6h). The brains of sham-treated animals were collected at 2 h after treatment(VMH_sham). The VMH was microdissected from dehydrated brain sections, and its total RNA was extracted. RNA samples from two or three animals were pooled to minimize the impact of biological variance. After nucleotide amplification by the ovation amplification, the gene expression profiles were obtained by the Affymetrix microarray analysis. The microarray analysis was performed twice using different sets of animals.
Project description:Microdissected ventromedial hypothalamus (VMH) was profiled to identify transcriptional changes after Nkx2-1 ablation in female mice. Total RNA was extracted from conditional mutants (Nkx2-1 f/f; Sf1Cre) and floxed controls (Nkx2-1 f/f) at postnatal day 10 (P10) and profiled using Mouse ref8 v2.0 Illumina chips and reagents (n=4/group).
