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STAT3 in the dorsal raphe gates behavioural reactivity and regulates gene networks associated with psychopathology

ABSTRACT: STAT3 in the dorsal raphe gates behavioural reactivity and regulates gene networks associated with psychopathology

PROVIDER: PRJNA609297 | ENA |

REPOSITORIES: ENA

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STAT3 in the dorsal raphe gates behavioural reactivity and regulates gene networks associated with psychopathology

Project description:The signal transducer and activator of transcription 3 (STAT3) signalling pathway is activated through phosphorylation by Janus kinases in response to a diverse set of immunogenic and non-immunogenic triggers. Several distinct lines of evidence propose an intricate involvement of STAT3 in neural function relevant to behaviour in health and disease. However, in part due to the pleiotropic effects resulting from its DNA binding activity and the consequent regulation of expression of a variety of genes with context-dependent cellular consequences, the precise nature of STAT3 involvement in the neural mechanisms underlying psychopathology remains incompletely understood. Here, we focussed on the midbrain serotonergic system, a central hub for the regulation of emotions, to examine the relevance of STAT3 signalling for emotional behaviour in mice by selectively knocking down raphe STAT3 expression using germline genetic (STAT3 KO) and viral-mediated approaches. Mice locally lacking STAT3 presented with reduced negative behavioural reactivity and a blunted response to the sensitising effects of amphetamine, alongside alterations in midbrain neuronal firing activity of serotonergic neurons and transcriptional control of gene networks relevant for neuropsychiatric disorders. Viral knockdown of dorsal raphe (DR) STAT3 phenocopied the behavioural alterations of STAT3 KO mice, excluding a developmentally determined effect and suggesting that disruption of STAT3 signalling in the DR of adult mice is sufficient for the manifestation of behavioural traits relevant to psychopathology. Collectively, these results suggest DR STAT3 as a molecular gate for the control of behavioural reactivity, constituting a mechanistic link between the immune system, serotonergic neurotransmission and psychopathology.

2020-02-29 | GSE146101 | GEO

mRNA profiles from dorsal raphe and amygdala of high-responder and low-responder rats

Project description:We identified 271 transcripts as differentially regulated in the dorsal raphe and/or the amygdala of high-responder and low-responder rats

2017-03-12 | GSE86893 | GEO

microRNA profiles from dorsal raphe and amygdala of high-responder and low-responder rats

Project description:We report 33 microRNAs are differentially expressed in the dorsal raphe and/or amygdala of rats selectively bred for high and low locomotor response to novelty (high responder and low responder rats)

2017-03-12 | GSE86934 | GEO

Effect of Ovarian Hormone on Gene Expression in Rhesus Dorsal Raphe Nucleus with Rhesus Affymetrix Chip

Project description:A small block of the midbrain containing the dorsal raphe nucleus was obtained from ovariectomized monkeys treated with placebo, estrogen, progesterone or estrogen plus progesterone for one month. The RNA was extracted and hybridized to the Rhesus Affymetrix chip. The results were analyzed with GCOS 1.0 Each chip represents one monkey. N=3 monkeys per treatment.

2010-04-09 | E-GEOD-16172 | biostudies-arrayexpress

Effect of Ovarian Hormone on Gene Expression in Rhesus Dorsal Raphe Nucleus with Human U95A Affymetrix Chip

Project description:Small blocks of the midbrain containing the dorsal raphe nucleus was obtained from ovariectomized monkeys treated with placebo, estrogen, progesterone or estrogen plus progesterone for one month. The RNA was extracted and hybridized to the human U95A Affymetrix chip. Each chip represents one monkey. N=3 monkeys per treatment.

2009-05-21 | E-GEOD-16171 | biostudies-arrayexpress

Effect of Ovarian Hormone on Gene Expression in Rhesus Dorsal Raphe Nucleus with Rhesus Affymetrix Chip

2009-05-21 | GSE16172 | GEO

Effect of Ovarian Hormone on Gene Expression in Rhesus Dorsal Raphe Nucleus with Human U95A Affymetrix Chip

2009-05-21 | GSE16171 | GEO

Molecular and anatomical organization of the dorsal raphe nucleus

Project description:Molecular and anatomical organization of the dorsal raphe nucleus

| PRJNA554121 | ENA

Molecular and anatomical organization of the dorsal raphe nucleus

Project description:The dorsal raphe nucleus (DRN) is an important source of neuromodulators and has been implicated in a wide variety of behavioral and neurological disorders. The DRN is subdivided into distinct anatomical subregions comprised of multiple cell types, and its complex cellular organization has impeded efforts to investigate the distinct circuit and behavioral functions of its subdomains. Here we used single-cell RNA sequencing, in situ hybridization, anatomical tracing, and spatial correlation analysis to map the transcriptional and spatial profiles of cells from the mouse DRN. Our analysis of 39,411 single-cell transcriptomes revealed at least 18 distinct neuron subtypes and 5 serotonergic neuron subtypes with distinct molecular and anatomical properties, including a serotonergic neuron subtype that preferentially innervates the basal ganglia. Our study lays out the molecular organization of distinct serotonergic and non-serotonergic subsystems, and will facilitate the design of strategies for further dissection the DRN and its diverse functions.

2019-08-06 | GSE134163 | GEO

Divergent transcriptional regulation of astrocyte reactivity across disorders [TR_ATAC_SCI]

Project description:Single-nuclei Assay for Transposase-Accessible Chromatin with sequencing (snATACseq) was applied to examine chromatin landscape changes and transcriptional regulator (TR) DNA motif accessibility in reactive astrocytes following traumatic spinal cord injury (SCI). Astrocyte nuclei were isolated from the spinal cord of wild type mice and mice with astrocyte-specific conditional gene deletion (cKO) of test-case TRs, SMARCA4 (Smarca4-astro-cKO) or STAT3 knockout (Stat3-astro-cKO). Comparison of differential chromatin accessibility revealed substantial remodeling during astrocyte reactivity, with more chromatin opening than closing. Marked alterations in access to SCI reactivity-associated TR motifs were also detected.

2022-05-26 | GSE199481 | GEO

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