Gene expression in groups of sympathetic neurons from an NPY reporter mouse
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE81075 | GEO | 2016/05/04
SECONDARY ACCESSION(S): PRJNA320420
REPOSITORIES: GEO
Similar Datasets
Project description:Neuropeptide Y (NPY) exerts powerful feeding related functions in the hypothalamus. However, NPY is also present in extra-hypothalamic nuclei, however their influence on energy homeostasis is unclear. Here we uncover a previously unknown feeding stimulatory pathway that is activated under conditions of stress in combination with calorie dense food with NPY neurons in the central amygdala (CeA) being responsible for an exacerbated response to a combined stress and high fat diet intervention. CeA NPY neuron specific Npy overexpression mimics the obese phenotype seen in a stress/HFD model, which is prevented by the selective ablation of Npy. Using food intake and energy expenditure (EE) as readout we demonstrate that selective activation of CeA NPY neurons results in increased food intake and a decrease in EE, which requires the presence of NPY. Mechanistically it is the diminished insulin signalling capacity on CeA NPY neurons under stress combined with HFD conditions that leads to the exaggerated development of obesity.
2019-03-31 | GSE128413 | GEO
Project description:Cortical GABAergic interneurons have been shown to fulfil important roles by inhibiting excitatory principal neurons. Recent transcriptomic studies have confirmed seminal discoveries that used anatomical and electrophysiological methods highlighting the existence of multiple different classes of GABAergic interneurons. However, individual studies have rarely addressed regional specific differences in gene expression in a given subclass of neuron. Using single-cell Patch-RNAseq, we characterised neuropeptide Y (NPY)-positive GABAergic interneurons in superficial layers of the primary auditory cortex and in distal layers of area CA3. We found that more than 300 genes are differentially expressed in NPY-positive neurons between these two brain regions. For example, the AMPA receptor auxiliary subunit Shisa9/CKAMP44 and the 5-HT2a receptor are significantly higher expressed in auditory NPY-positive neurons. These findings guided us to perform pharmacological experiments that revealed a role for 5-HT2a receptors in auditory NPY-positive neurons. Specifically, although the application of 5-HT led to a depolarisation of both auditory and CA3 NPY-positive neurons, the 5-HT2a receptor antagonist ketanserin only reversed membrane potential changes in auditory NPY-positive neurons. Our study demonstrates the potential of single-cell transcriptomic studies in guiding directed pharmacological experiments.
2022-04-20 | GSE193293 | GEO
Project description:Neuropeptide Y (NPY) is an endogenous modulator of neuronal activity by regulating GABA and glutamate release. Previously, we found that estradiol modulates NPY expression in the hippocampal dentate gyrus. Here we investigated which estrogen receptor type activation is required for the NPY expression. Further, we determined effects of estrogen receptor activation on NPY release. Finally, we determined the contribution of estrogen-mediated remodeling of the GABAergic and glutamatergic network in relation to changes in coupling with NPY in ovariectomized rats. We found that activation of either estrogen receptor type increases NPY expression as well as NPY release in the dentate gyrus. We also found that compared to OVX rats, estrogen replacement increases the likeness of synergistic/antagonistic coupling between the NPY and GABAergic synapse genes while the glutamatergic synapse genes are less likely coupled with NPY. The data together suggest that estrogen plays a critical role in regulation of activity of the NPY system and its coupling to GABAergic and glutamatergic synapses in female rat dentate gyrus. Two-conditions (E = beta-estradiol replacement vs O = oil) experiment. Biological replicates: 4E, 4O.
2014-08-02 | E-GEOD-60013 | biostudies-arrayexpress
Project description:Neuropeptide Y (NPY) is an endogenous modulator of neuronal activity by regulating GABA and glutamate release. Previously, we found that estradiol modulates NPY expression in the hippocampal dentate gyrus. Here we investigated which estrogen receptor type activation is required for the NPY expression. Further, we determined effects of estrogen receptor activation on NPY release. Finally, we determined the contribution of estrogen-mediated remodeling of the GABAergic and glutamatergic network in relation to changes in coupling with NPY in ovariectomized rats. We found that activation of either estrogen receptor type increases NPY expression as well as NPY release in the dentate gyrus. We also found that compared to OVX rats, estrogen replacement increases the likeness of synergistic/antagonistic coupling between the NPY and GABAergic synapse genes while the glutamatergic synapse genes are less likely coupled with NPY. The data together suggest that estrogen plays a critical role in regulation of activity of the NPY system and its coupling to GABAergic and glutamatergic synapses in female rat dentate gyrus.
2014-08-02 | GSE60013 | GEO
Project description:Microarrays were used to examine gene expression changes between two hypothalamic cell lines derived from adult and embryonic tissues. Both cell lines endogenously express the protein Npy (neuropeptide y) which is involved in feeding and reproductive processes. Results identify novel gene candidates that are implicated in the development of hypothalamic sub-poplulations.
2012-06-01 | GSE30467 | GEO
Project description:Microarrays were used to examine gene expression changes between two hypothalamic cell lines derived from adult and embryonic tissues. Both cell lines endogenously express the protein Npy (neuropeptide y) which is involved in feeding and reproductive processes. Results identify novel gene candidates that are implicated in the development of hypothalamic sub-poplulations. Immortalized hypothalamic cell lines were created by overexpression of SV40 T-antigen from tissue sources derived from both embryonic and adult mice. Triplicate plates of each cell line were grown to 70% confluence and RNA was harvested for microarray analysis.
2012-05-31 | E-GEOD-30467 | biostudies-arrayexpress
Project description:The arcuate nucleus of the hypothalamus (ARH) is one key structure controlling energy homeostasis. While it has been shown that the biogenic amines dopamine and serotonin modulate food intake controlling NPY/AgRP and/or POMC neurons in the ARH, the neural substrates that mediate the effect of noradrenaline (NA) on energy homeostasis remain elusive. By electrophysiological recordings and cell type-specific transcriptomics we show that the main neuronal populations in the ARH, NPY/AgRP and POMC neurons express a combination of excitatory and inhibitory adrenergic receptors (ARs). Surprisingly, NA had a clear differential effect on these neurons. Activation of NPY/AgRP neurons is mediated by _1A - and _- ARs, while POMC neurons are inhibited via _2A ARs. Collectively, our data indicate an orexigenic influence of NA on the ARH circuitry that controls energy balance
2017-10-26 | GSE106188 | GEO
Project description:Neuropeptide Y (NPY) is a pleiotropic peptide produced in the central nervous system and peripheral organs. Despite conjectures that NPY may have a role in skin physiology and pathology, the effects of NPY in this organ remain poorly understood. We reported that a knock-in mouse with entopic NPY overexpression exhibits significantly elevated NPY in the skin, accompanied by premature and progressive hair graying secondary to depletion of melanocyte stem cells within hair follicles. However, the question remains as to whether NPY overexpression in the skin can induce non-melanocyte pathology. In this study, we employed this mouse to investigate consequences of skin-specific overexpression of NPY. Our findings show that chronic NPY overexpression in the skin induces dermal fibrosis and epidermal hyperkeratosis. Additionally, NPY overexpression induces significant accumulation of macrophages and T-regs in the dermis. RNA sequencing of whole skin from NPY-overexpressing mice further reveals NPY-mediated transcriptional changes consistent with inflammatory processes and inflammation-associated skin changes. Together, these results provide long-awaited evidence of NPY’s involvement in skin pathology, providing a background for future precise definition of its role in the regulation of cutaneous homeostasis.
2022-09-01 | GSE183831 | GEO
Project description:Purpose: The locus coeruleus (LC) is a small nucleus in the pons, with norepinephrine (NE) as its major transmitter. It plays key roles in wakefulness and is associated with disorders like depression. The study aims to analyze single-cell RNA-seq data to subdivide neurons in the LC and chart their neuropeptide, co-transmitter, and receptor profiles. It also seeks to build a precise map of galanin and its receptors in the mouse LC, and understand the role of neuropeptide expression and signaling. Results: The study identified 24 clusters in total, with 3 NE, 17 glutamate, and 5 GABA subtypes. NE neurons expressed at least 19 neuropeptide transcripts, mainly galanin (Gal) but not Npy, and >30 neuropeptide receptors. Among galanin receptors, Galr1 was expressed in ~19% of NE neurons, and highly expressed in GABA neurons surrounding the NE ensemble. Patch-clamp electrophysiology and cell-type-specific Ca2+-imaging using GCaMP6s revealed that a GalR1 agonist inhibits no more than ~35% of NE neurons, with the effect being direct and not relying on feed-forward GABA inhibition. Conclusions: The results define a role for the galanin system in NE functions and provide a conceptual framework for the action of many other peptides and their receptors. The study found that most NE neurons express mRNA transcripts for galanin, at least 19 neuropeptides (but not Npy), and >30 neuropeptide receptors, including Galr1 at low levels. Selective activation of GalR1 inhibited the spontaneous activity of a subset of NE neurons possibly through the activation of Kv currents. These findings offer new insights into the role of neuropeptide expression and signaling in mouse LC.
2023-07-03 | GSE236349 | GEO
Project description:Neuropathic pain is a refractory condition that involves de novo protein synthesis in the nociceptive pathway. The mechanistic target of rapamycin (mTOR) is a master regulator of protein synthesis; however, mechanisms underlying its role in neuropathic pain remain elusive. Using spared nerve injury-induced neuropathic pain model, we found mTOR activation in large-diameter dorsal root ganglion (DRG) neurons and spinal microglia. However, selective ablation of mTOR in DRG neurons, rather than microglia, alleviated neuropathic pain. Combining transcriptomic profiling, electrophysiological recording and pharmacologic manipulations, we demonstrated that activated mTOR promoted neuropeptide Y (NPY) induction in mechanoreceptors and that NPY acted on Y2 receptors (Y2R) but not Y1R to enhance nociceptor excitability. Peripheral replenishment of NPY reversed pain alleviation upon mTOR removal, whereas Y2R antagonists prevented its function. Our findings reveal an unexpected link between mTOR and NPY in promoting nociceptor sensitization and neuropathic pain, through NPY/Y2R signaling-mediated intra-ganglionic transmission.
2022-09-01 | GSE184014 | GEO