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Distinct mechanisms of non-autonomous UPRER mediated by GABAergic, glutamatergic, and octopaminergic neurons

ABSTRACT: Distinct mechanisms of non-autonomous UPRER mediated by GABAergic, glutamatergic, and octopaminergic neurons

PROVIDER: PRJEB76195 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR13179216_1.fastq.gz	Fastqsanger.gz
	ERR13179216_2.fastq.gz	Fastqsanger.gz
	ERR13179217_1.fastq.gz	Fastqsanger.gz
	ERR13179217_2.fastq.gz	Fastqsanger.gz
	ERR13179218_1.fastq.gz	Fastqsanger.gz

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Distinct mechanisms of non-autonomous UPRER mediated by GABAergic, glutamatergic, and octopaminergic neurons

Project description:The capacity to deal with stress declines during the aging process, and preservation of cellular stress responses is critical to healthy aging. The unfolded protein response of the endoplasmic reticulum (UPRER) is one such conserved mechanism which is critical for the maintenance of several major functions of the ER during stress, including protein folding and lipid metabolism. Hyperactivation of the UPRER by overexpression of the major transcription factor, xbp-1s, solely in neurons drives lifespan extension as neurons send a neurotransmitter-based signal to other tissue to activate UPRER in a non-autonomous fashion. Previous work identified serotonergic and dopaminergic neurons in this signaling paradigm. To further expand our understanding of the neural circuitry that underlies the non-autonomous signaling of ER stress, we activated UPRER solely in glutamatergic, octopaminergic, and GABAergic neurons in C. elegans and paired whole-body transcriptomic analysis with functional assays. We found that UPRER-induced signals from glutamatergic neurons increased expression of canonical protein homeostasis pathways and octopaminergic neurons promoted pathogen response pathways, while minor, but statistically significant changes were observed in lipid metabolism-related genes with GABAergic UPRER activation. These findings provide further evidence for the distinct role neuronal subtypes play in driving the diverse response to ER stress.

2024-06-15 | E-MTAB-14132 | biostudies-arrayexpress

Common schizophrenia risk variants are implicated in the function of glutamatergic neurons

Project description:The epigenome of human brain cells encompasses key information in understanding brain function in both healthy and diseased states. To further explore this, we used ATAC-seq to profile chromatin structure in four distinct populations of cells (glutamatergic neurons, GABAergic neurons, oligodendrocytes, and microglia/astrocytes), from three different regions of the brain. Chromatin accessibility was found to vary vastly by cell type and, more moderately, by brain region, with glutamatergic neurons showing the greatest regional variability. Transcription factor footprinting pointed to cell-specific transcriptional regulators and inferred cell-specific regulation of protein coding genes, long intergenic noncoding RNAs, and microRNAs. In vivo transgenic mouse experiments validated the cell type specificity of a number of human-derived regulatory sequences. Open chromatin regions in glutamatergic neurons were enriched for neuropsychiatric risk variants, particularly those associated with schizophrenia. Combining differential chromatin accessibility analysis using ATAC-seq data from bulk tissue increased our statistical power to confirm glutamatergic neurons as the cell type most affected in schizophrenia. Jointly, these findings illustrate the utility of studying the cell type specific epigenome in complex tissues such as the human brain and implicate an association among chromatin accessibility in glutamatergic neurons and genetic risk for schizophrenia.

2020-08-20 | GSE143666 | GEO

Subcellular Single Cell Sequencing: mRNA Diversity of Individual Glutamatergic and GABAergic Hippocampal Neurons and their Dendrites.

Project description:Subcellular Single Cell Sequencing: mRNA Diversity of Individual Glutamatergic and GABAergic Hippocampal Neurons and their Dendrites.

| PRJNA660436 | ENA

Sustained antidepressant effects of ketamine metabolite involve GABAergic inhibition-mediated molecular dynamics in aPVT glutamatergic neurons

Project description:Sustained antidepressant effects of ketamine metabolite involve GABAergic inhibition-mediated molecular dynamics in aPVT glutamatergic neurons

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Identification of genes involved in GABAergic Wiring

Project description:How neurons are wired to form precise circuits is crucial to understand the development of cortical functions. Glutamatergic pyramidal cell and GABAergic interneuron wire up the cortex through differentiated cellular events. However, little is known about the molecular mechanisms that underlie the unique features of interneuron wiring. We performed a high-throughput genomic screen for genes upregulated specifically during GABAergic wiring.

2018-07-31 | GSE115948 | GEO

Loss of the parkinsonism-associated protein FBXO7 in glutamatergic forebrain neurons in mice leads to anormal motor behavior and synaptic defects

Project description:Mutations in PARK15, which encodes for the F-box protein FBXO7 have been associated with Parkinsonian Pyramidal syndrome, a rare and complex movement disorder with Parkinsonian symptoms, pyramidal tract signs and juvenile onset. Our previous study showed that systemic loss of Fbxo7 in mice causes motor defects and premature death. We have also demonstrated that FBXO7 has a crucial role in neurons as the specific deletion in tyrosine hydroxylase-positive or glutamatergic forebrain neurons leads to late-onset or early-onset motor dysfunction, respectively. In this study, we examined NEXCre; Fbxo7fl/fl mice, in which Fbxo7 was specifically deleted in glutamatergic projection neurons. The effects of FBXO7 deficiency on striatal integrity were investigated with HPLC and histological analyses. NEX-Cre;Fbxo7fl/fl mice revealed an increase in striatal dopamine concentrations, changes in the glutamatergic, GABAergic and dopaminergic pathways, astrogliosis and microgliosis and little or no neuronal loss in the striatum. To determine the effects on the integrity of the synapse, we purified synaptic membranes, subjected them to quantitative mass spectrometry analysis and found alterations in the complement system, endocytosis and exocytosis pathways. These neuropathological changes coincide with alterations in spontaneous home cage behavior. Taken together, our findings suggest that FBXO7 is crucial for corticostriatal projections and the synaptic integrity of the striatum, and consequently for proper motor control.

2023-09-18 | PXD044119 | Pride

Sex-Specific and Opposed Effects of FKBP51 in Glutamatergic and GABAergic Neurons: Implications for Stress Susceptibility and Resilience

Project description:Mental health disorders often arise as a combination of environmental and genetic factors. The FKBP5 gene, encoding the GR co-chaperone FKBP51, has been uncovered as a key genetic risk factor for stress related illness. However, the exact cell type and region-specific mechanisms by which FKBP51 contributes to stress resilience or susceptibility processes remain to be unravelled. FKBP51 functionality is known to interact with the environmental risk factors age and sex, but so far data on behavioral, structural and molecular consequences of these interactions are still largely unknown. Here we report the cell type- and sex-specific contribution of FKBP51 to stress susceptibility and resilience mechanisms under the high-risk environmental conditions of an older age, by using two conditional knockout models within glutamatergic (Fkbp5Nex) and GABAergic (Fkbp5Dlx) neurons of the forebrain. Specific manipulation of Fkbp5 in these two cell types led to opposing effects on behavior, brain structure and gene expression profiles in a highly sex-dependent fashion. The results emphasize the role of FKBP51 as a key player in stress-related illness and the need for more targeted and sex-specific treatment strategies.

2023-05-16 | GSE232460 | GEO

Sex-Specific and Opposed Effects of FKBP51 in Glutamatergic and GABAergic Neurons: Implications for Stress Susceptibility and Resilience

Project description:Sex-Specific and Opposed Effects of FKBP51 in Glutamatergic and GABAergic Neurons: Implications for Stress Susceptibility and Resilience

| PRJNA972070 | ENA

Gene expression profiling of GABAergic neurons isolated from different brain regions

Project description:The main goal of the experiment was to analize the transcriptome of GABAergic neurons in general and compare their expression profiles among different brain regions Keywords: GABAergic neurons; expression profiling; rare cell

2008-08-12 | GSE8984 | GEO

Single-nucleus transcriptional profiling of Gad2-positive neurons from the mouse lateral habenula with distinct expression of neurotransmitter-related genes

Project description:Glutamatergic projection neurons of the lateral habenula (LHb) effect behavioral statemodulation by regulating the activity of midbrain monoaminergic neurons. Identifying circuit mechanisms that control LHb output is of interest for understanding motivated behaviors. A small population of neurons within the medial subnucleus of the mouse LHb express the GABAergic synthesizing enzyme GAD2 and are capable of inhibiting nearby LHb projection neurons. However, these neurons lack most markers of classic inhibitory interneurons, and they co-express the vesicular glutamate transporter VGLUT2. To determine the molecular phenotype of these neurons, we genetically tagged the nuclei of GAD2-positive cells and used fluorescence-activated nuclear sorting followed by single nuclear RNA sequencing (FANS-snRNAseq) to determine the full transcriptional profile of GAD2+ neurons isolated from LHb. Our data demonstrate that LHb GAD2+ neurons co-express markers of both glutamatergic and GABAergic transmission and that they are transcriptionally distinct from GABAergic interneurons or habenular glutamatergic neurons. We show sex-specific differences in gene expression in this neuronal population and find that these gene sets are enriched for genes involved in depression. Finally, we identify the Ntng2 gene encoding the cell adhesion protein Netrin-G2 as a selective marker of LHb GAD2+ neurons that may contribute to their target projections. These data show the value of using genetic enrichment of rare cell types for transcriptome studies, and they advance understanding of the molecular composition of a functionally important class of neurons in the LHb.

2022-11-08 | GSE179198 | GEO

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