SNORD90 induces glutamatergic signaling following treatment with monoaminergic antidepressants
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA929492 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23271000.fastq.gz | Fastqsanger.gz | |||
| SRR23271100.fastq.gz | Fastqsanger.gz | |||
| SRR23271200.fastq.gz | Fastqsanger.gz | |||
| SRR23271300.fastq.gz | Fastqsanger.gz | |||
| SRR23271400.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 516 |
Similar Datasets
Project description:Pharmacotherapies for the treatment of major depressive disorder were serendipitously discovered almost seven decades ago. From this discovery, scientists pinpointed the monoaminergic system as the primary target associated with symptom alleviation. As a result, most antidepressants have been engineered to act on the monoaminergic system more selectively, primarily on serotonin, in an effort to increase treatment response and reduce unfavorable side effects. However, slow and inconsistent clinical responses continue to be observed with these available treatments. Recent findings point to the glutamatergic system as a target for rapid acting antidepressants. Investigating different cohorts of depressed individuals treated with serotonergic and other monoaminergic antidepressants, we found that the expression of a small nucleolar RNA, SNORD90, was elevated following treatment response. When we increased Snord90 levels in the mouse anterior cingulate cortex (ACC), a brain region regulating mood responses, we observed antidepressive-like behaviors. We identified neuregulin 3 (NRG3) as one of the targets of SNORD90, which we show is regulated through the accumulation of N6-methyladenosine modifications leading to YTHDF2-mediated RNA decay. We further demonstrate that a decrease in NRG3 expression resulted in increased glutamatergic release in the mouse ACC. These findings support a molecular link between monoaminergic antidepressant treatment and glutamatergic neurotransmission.
| S-EPMC10335830 | biostudies-literature
Project description:To investigate the role of small nucleolar RNAs in the context of antidepressant response and major depressive disorder
2023-07-11 | GSE224050 | GEO
Project description:Ten-eleven translocation (Tet) is an important gene in neurodevelopment, but how Tet regulates brain development is still under study. Mutations in human TET proteins have been found in individuals with neurodevelopmental disorders. Here we report a new function of Tet in regulating Drosophila early brain development. We found that mutation on the Tet DNA-binding domain (TetAXXC) resulted in axon guidance defects in the mushroom body (MB). Tet is required in early brain development during the outgrowth of MB β axons. Transcriptomic study of TetAXXC mutant and wild-type pupal brains shows that glutamine synthetase 2 (Gs2), a key enzyme in glutamatergic signaling, is the most significantly down-regulated gene in the Tet mutant brains. RNAi knockdown or CRISPR/Cas9 mutagenesis of Gs2 recapitulates the TetAXXC phenotype. Surprisingly, Tet and Gs2 act in the insulin-producing cells (IPCs) to control MB axon guidance, and overexpression of Gs2 in the IPCs rescue the axonal defects of TetAXXC. Treating TetAXXC with the metabotropic glutamate receptor antagonist MPEP can also rescue the phenotype confirming Tet function in regulating glutamatergic signaling. TetAXXC and the Drosophila homolog of Fragile X Messenger Ribonucleoprotein protein mutant (Fmr13) have similar mushroom body axonal defects and reduction in Gs2 transcription, and, importantly, overexpression of Gs2 in the IPCs of Fmr1 mutants also rescues the axonal defects. Our studies reveal a new function of Tet in regulating axon guidance in the brain via glutamatergic signaling and suggest overlapping functions between Tet and Fmr1.
2024-04-20 | GSE231534 | GEO
Project description:Tet Controls Axon Guidance in Early Brain Development through Glutamatergic Signaling
| PRJNA966247 | ENA
Project description:Interactions among neuroglial and vascular components are crucial for retinal angiogenesis and blood-retinal barrier (BRB) maturation. Neuronal synaptic dysfunctions precede vascular abnormalities in many retinal pathologies. However, whether neuronal activity, specifically glutamatergic activity, regulates retinal angiogenesis and BRB maturation remains unclear. Using in vivo genetic studies in mice, single-cell RNA-sequencing and functional validation, we found that deep plexus angiogenesis and paracellular BRB maturation are delayed in Vglut1-/- retinas, where neurons fail to release glutamate. In contrast, deep plexus angiogenesis and paracellular BRB maturation are accelerated in Gnat1-/- retinas, where constitutively depolarized rods release excess glutamate. Mechanistically, Norrin expression and endothelial Norrin/b-catenin signaling are downregulated in Vglut1-/- retinas, and upregulated in Gnat1-/- retinas. Pharmacological activation of endothelial Norrin/ b-catenin signaling in Vglut1-/- retinas rescued both deep plexus angiogenesis and paracellular BRB integrity. Thus, our findings demonstrate that glutamatergic neuronal activity regulates retinal angiogenesis and BRB maturation by modulating Norrin/b-catenin signaling.
2024-06-27 | GSE235993 | GEO
Project description:Alpha-synuclein (aSyn) is a central player in the pathogenesis of synucleinopathies due to its accumulation in typical protein aggregates in the brain. However, it is still unclear how it contributes to neurodegeneration. Type-2 diabetes mellitus is a risk factor for Parkinson’s disease (PD) and, interestingly, a common molecular alteration among these disorders is the age-associated increase in protein glycation. We hypothesized that glycation-induced neuronal dysfunction might be a contributing factor in synucleinopathies. Here, we dissected the specific impact of methylglyoxal (MGO, a glycating agent) in mice overexpressing aSyn in the brain. We found that MGO-glycation potentiates motor, cognitive, olfactory, and colonic dysfunction in aSyn transgenic (Thy1-aSyn) mice that received a single dose of MGO via intracerebroventricular (ICV) injection. aSyn accumulates in the midbrain, striatum, and prefrontal cortex, and protein glycation is increased in the cerebellum and midbrain. SWATH mass spectrometry analysis, used to quantify changes in the brain proteome, revealed that MGO mainly increase glutamatergic-associated proteins in the midbrain (NMDA, AMPA, glutaminase, VGLUT and EAAT1), but not in the prefrontal cortex, where it mainly affects the electron transport chain. Notably, the glycated proteins in the midbrain of Thy1-aSyn mice that received MGO strongly correlate with PD and dopaminergic pathways. Overall, we demonstrated that MGO-induced glycation accelerates PD-like sensorimotor and cognitive alterations and suggest that the increase of glutamatergic signaling may underly these events. Our study sheds new light into the enhanced vulnerability of the midbrain in PD-related synaptic dysfunction and suggests that glycation suppressors and anti-glutamatergic drugs may hold promise as disease-modifying therapies for synucleinopathies.
2022-05-20 | PXD032832 | Pride
Project description:Gene expression profiles of glutamatergic neuron progenitors (Neurod6-positive cells)
2012-12-08 | E-MTAB-893 | biostudies-arrayexpress
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
Project description:Frontotemporal dementia (FTD) due to MAPT mutation causes pathological accumulation of tau and glutamatergic cortical neuronal death by unknown mechanisms. We used human induced pluripotent stem cell (iPSC)-derived cerebral organoids expressing tau-V337M and isogenic corrected controls to discover early alterations due to the mutation that precede neurodegeneration. Mutant organoids show early upregulation of MAPT expresssion and glutamatergic signaling pathways, as well as regulators including the RNA-binding protein ELAVL4. By 6 months, tau-V337M organoids show specific loss of glutamatergic neuronsof layers affected in patients. Mutant neurons are susceptible to glutamate toxicity, which was rescued pharmacologically by treatment with the PIKFYVE kinase inhibitor apilimod. Our results demonstrate a sequence of events that precede cell death, revealing molecular pathways associated with glutamate signaling as potential targets for therapeutic intervention in FTD.
2021-07-26 | GSE171344 | GEO
Project description:Frontotemporal dementia (FTD) due to MAPT mutation causes pathological accumulation of tau and glutamatergic cortical neuronal death by unknown mechanisms. We used human induced pluripotent stem cell (iPSC)-derived cerebral organoids expressing tau-V337M and isogenic corrected controls to discover early alterations due to the mutation that precede neurodegeneration. Mutant organoids show early upregulation of MAPT expresssion and glutamatergic signaling pathways, as well as regulators including the RNA-binding protein ELAVL4. By 6 months, tau-V337M organoids show specific loss of glutamatergic neuronsof layers affected in patients. Mutant neurons are susceptible to glutamate toxicity, which was rescued pharmacologically by treatment with the PIKFYVE kinase inhibitor apilimod. Our results demonstrate a sequence of events that precede cell death, revealing molecular pathways associated with glutamate signaling as potential targets for therapeutic intervention in FTD.
2021-07-26 | GSE171343 | GEO