Estrogen receptor-α expressing neurons in the ventrolateral VMH regulate glucose balance
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PROVIDER: PRJNA610836 | ENA |
REPOSITORIES: ENA
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Project description:Background: Brain glucose-sensing neurons detect glucose fluctuations and prevent severe hypoglycemia, but mechanisms mediating functions of these glucose-sensing neurons are unclear. Methods: We combined mouse genetics, electrophysiology, neural tracing, optogenetics and Patch-RNA-seq to demonstrate how glucose-sensing neurons in the ventrolateral VMH regulate glucose balance. Results: Here we report that estrogen receptor-α (ERα)-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH) are glucose-sensing neurons to a 5-1-5mM glucose fluctuation, being glucose-inhibited neurons (GI-ERαvlVMH) or glucose-excited neurons (GE-ERαvlVMH). Hypoglycemia activates GI-ERαvlVMH neurons via the anoctamin 4 channel, and inhibits GE-ERαvlVMH neurons through opening the ATP-sensitive potassium channel. Further, we show that GI-ERαvlVMH neurons preferentially project to the medioposterior arcuate nucleus of the hypothalamus (mpARH) and GE-ERαvlVMH neurons preferentially project to the dorsal Raphe nuclei (DRN). Activation of ERαvlVMH-mpARH circuit and inhibition of ERαvlVMH-DRN circuit both increase blood glucose. Conclusions: Our results indicate that ERαvlVMH neurons detect glucose fluctuations and prevent severe hypoglycemia in mice.
2020-04-01 | GSE146543 | GEO
Project description: Not available
| S-EPMC7195451 | biostudies-literature
Project description:Estrogen receptor a (ERa) signaling in the ventromedial hypothalamus (VMH) contributes to energy homeostasis by modulating physical activity and thermogenesis. However, the precise neuronal populations involved remain undefined. Using single-cell RNA transcriptomics and in situ hybridization, we describe six neuronal populations in the mouse VMH. ERa is enriched in populations showing sex biased expression of reprimo (Rprm), tachykinin 1 (Tac1), and prodynorphin (Pdyn). Female biased expression of Tac1 and Rprm is patterned by ERa-dependent repression during male development, whereas male biased expression of Pdyn is maintained by circulating testicular hormone in adulthood. Chemogenetic activation of ERa+ VMH neurons stimulates heat generation and movement in both sexes. However, silencing Rprm gene function increases core temperature selectively in females and ectopic Rprm expression in males is associated with reduced core temperature. Together these findings reveal a role for Rprm in temperature regulation and ERa in the masculinization of neuron populations that underlie energy expenditure.
2020-04-01 | GSE143818 | GEO
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.
2012-05-29 | E-GEOD-38311 | biostudies-arrayexpress
Project description:To identify transcripts enriched in ventomedial hypothalamus (VMH) neurons, we used translating affinity ribosome purification combined with RNA-seq (TRAP-seq) from Nr5a1-Cre mice.
2021-05-19 | GSE172206 | GEO
Project description:To identify transcripts enriched in ventomedial hypothalamus (VMH) Lepr neurons, we used translating affinity ribosome purification combined with RNA-seq (TRAP-seq) from Lepr-Cre mice.
2021-05-19 | GSE172200 | GEO
Project description:To identify genes selectively expressed in the DMH, we collected RNA samples from four hypothalamic nuclei, namely the Arc, VMH, DMH and LH, using laser microdissection and conducted microarray analysis to compare their gene expression profiles. The Arc, VMH, DMH, and LH were dissected from C57BL/6 females at 3 month of age by laser microdissection using the Leica 6000 system (n=2 each group).
2015-01-15 | E-GEOD-58238 | biostudies-arrayexpress
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.
2012-05-30 | GSE38311 | GEO
Project description:The Estrogen Receptor alpha (ERα) controls key cellular functions in hormone responsive breast cancer by assembling in large functional multiprotein complexes. ERα ligands are classified as agonists and antagonist, according to the response they elicit, thus the molecular characterization of the of ERα nuclear iteractome composition following estrogen and antiestrogen stimulation whose is needed to understand their effects on estrogen target tissues, in particular breast cancer. To this aim interaction proteomics coupled to mass spectrometry (MS) was applied to map the ERα nuclear interacting partners in MCF7 breast cancer cell nuclei following estrogen and antiestrogen stimuli.
2020-09-02 | PXD018709 | Pride
Project description:It is proposed that the impaired sympathoadrenal response to hypoglycemia induced by recurrent insulin-induced hypoglycemia (RH) is an adaptive phenomenon induced by specific changes in microRNA expression in the ventromedial hypothalamus (VMH). To test this hypothesis, genome-wide microRNAomic profiling of the VMH by RNA-sequencing was performed in control and RH treated rats. Differential expression analysis identified microRNA-7a-5p and microRNA-665 as potential mediators of this phenomenon. To further test this hypothesis, experiments were conducted consisting of targeted lentiviral-mediated overexpression of microRNA-7a-5p and downregulation of microRNA-665 in the VMH. Hyperinsulinemic hypoglycemic clamp experiments demonstrated that targeted overexpression of microRNA-7a-5p (but not downregulation of microRNA-665) in the VMH of RH rats restored the epinephrine response to hypoglycemia. This restored response to hypoglycemia was associated with a restoration of GABAA receptor gene expression. Finally, a direct interaction of microRNA-7a-5p with 3’-UTR of GABAA receptor α1-subunit (Gabra1) gene was demonstrated in a luciferase assay. These findings indicate that 1) the impaired sympathoadrenal response induced by RH is associated with changes in VMH microRNA expression, and 2) microRNA-7a-5p, possibly via direct downregulation of GABA receptor gene expression, may serve as a mediator of the altered sympathoadrenal response to hypoglycemia.
2019-10-17 | GSE138472 | GEO