Organ-specific Sympathetic Innervation Defines Visceral Functions
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE278457 | GEO | 2024/10/02
REPOSITORIES: GEO
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Project description:Organ-specific Sympathetic Innervation Defines Visceral Functions
| PRJNA1167307 | ENA
Project description:Regulation of membrane receptors involves management of endocytosis. At the neuromuscular junction, the synapse between skeletal muscle and motoneuron, proper density of the major receptor, the acetylcholine receptor, is of utmost importance for sustaining life in context of mobility. Recent work has revealed innervation of NMJs by sympathetic neurons and destruction of them had morphological and functional consequences, suggesting influence on endocytosis. To investigate the pathways and proteins that are relevant for acetylcholine receptor turnover and affected by sympathetic signaling, proteomes of mouse hindlimb muscles from sympathectomized and saline-treated control muscles were compared. Using proteomic, Western blot, and immunofluorescence analysis in chemically sympathectomized mouse hindlimb muscles, the cause of these consequences were aimed to analyzed. This revealed extensive regulation of the proteome by the sympathetic nervous system and a possible regulatory function of the endo/lysosomal and autophagic pathway by sympathetic neuronal input. This finding might provide a new explanation to the observed benefit of sympathicomimetic treatment in several congenital myasthenic syndromes.
2021-03-01 | PXD021601 | Pride
Project description:Dysregulation of glucagon secretion in type 1 diabetes (T1D) involves hypersecretion during postprandial states, but insufficient secretion during hypoglycemia. The sympathetic nervous system regulates glucagon secretion. To investigate islet sympathetic innervation in T1D, sympathetic tyrosine hydroxylase (TH) axons were analyzed in control non-diabetic organ donors, non-diabetic islet autoantibody-positive individuals (AAb), and age-matched persons with T1D. Islet TH axon numbers and density were significantly decreased in AAb compared to T1D with no significant differences observed in exocrine TH axon volume or lengths between groups. TH axons were in close approximation to islet α-cells in T1D individuals with long-standing diabetes. Islet RNA-sequencing and qRT-PCR analyses identified significant alterations in noradrenalin degradation, α-adrenergic signaling, cardiac b-adrenergic signaling, catecholamine biosynthesis, and additional neuropathology pathways. The close approximation of TH axons at islet α-cells supports a model for sympathetic efferent neurons directly regulating glucagon secretion. Sympathetic islet innervation and intrinsic adrenergic signaling pathways could be novel targets for improving glucagon secretion in T1D.
2021-08-09 | GSE181674 | GEO
Project description:Empirical and anecdotal evidence have associated stress with accelerated hair greying (formation of unpigmented hairs), but the scientific evidence linking the two is scant. Here, we report that acute stress leads to hair greying through fast depletion of melanocyte stem cells (MeSCs). Combining adrenalectomy, denervation, chemogenetics, cell ablation, and MeSC-specific adrenergic receptor knockout, we found that stress-induced MeSC loss is independent of immune attack or adrenal stress hormones. Rather, hair greying results from activation of the sympathetic nerves that innervate the MeSC niche. Upon stress, sympathetic nerve activation leads to burst release of the neurotransmitter norepinephrine, which drives quiescent MeSCs into rapid proliferation, followed by differentiation, migration, and permanent depletion from the niche. Transient suppression of MeSC proliferation prevents stress-induced hair greying. Our studies demonstrate that acute stress-induced neuronal activity can drive rapid and permanent loss of somatic stem cells, and illustrate an example in which somatic stem cell maintenance is directly influenced by the overall physiological state of the organism.
2019-11-28 | GSE131566 | GEO
Project description:Sympathetic nerves that innervate lymphoid organs regulate immune development and function by releasing norepinephrine (NE) that is sensed by immune cells via their expression of adrenergic receptors (ARs). Here, we demonstrate that ablation of SNS signaling suppresses tumor immunity, and we dissect the mechanism of such immune suppression. We report that disruption of the SNS in mice removes a critical α-adrenergic signal required for maturation of myeloid cells in normal as well as tumor-bearing mice. In tumor-bearing mice, disruption of the α-adrenergic signal leads to the accumulation of immature myeloid-derived suppressor cells (MDSC) that suppress tumor immunity and promote tumor growth. Furthermore, we show that these SNS-responsive MDSCs drive expansion of regulatory T cells via secretion of the alarmin heterodimer S100A8/A9, thereby compounding their immunosuppressive activity. Our results describe a regulatory framework in which sympathetic tone controls the development of innate and adaptive immune cells and influences their activity in health and disease.
2020-09-01 | GSE154973 | GEO
Project description:Adrenal chromaffin cells and sympathetic neuron are derived from neural crest precursors and both cell types can give rise to childhood cancer, neuroblastoma. However only limited is known about the mechanism of their development. Better understanding of their transcriptomic profiles during development could gives an insight into the cell fates acquisition as well as the origin of neuroblastoma. Yellow fluorescent protein expressing sympathetic neuroblasts and adrenal chromaffin cells were isolated from E12.5 TH-IRES-Cre;ROSA26-EYFP mouse embryos by fluorescence-activated cell sorting. Transcriptomic profiles of sympathetic neuroblasts and adrenal chromaffin cells from embryonic age (E)12.5 TH-IRES-Cre;ROSA26-EYFP mice were generated by RNA sequencing, in four paired biological replicates.
2019-05-24 | E-MTAB-7086 | biostudies-arrayexpress
Project description:The cell bodies of postganglionic sympathetic neurons innervating the heart primarily reside in the stellate ganglion (SG), alongside neurons innervating other organs and tissues. Whether cardiac-innervating stellate ganglionic neurons (SGNs) exhibit diversity and distinction from those innervating other tissues is not known. To identify and resolve the transcriptomic profiles of SGNs innervating the heart we leveraged retrograde tracing techniques using adeno-associated virus (AAV) expressing fluorescent proteins (GFP or Td-tomato) with single cell RNA sequencing. We investigated electrophysiologic, morphologic, and physiologic roles for subsets of cardiac-specific neurons and found that three of five adrenergic SGN subtypes innervate the heart. These three subtypes stratify into two subpopulations; high (NA1a) and low (NA1b and NA1c) Npy-expressing cells, exhibit distinct morphological, neurochemical, and electrophysiologic characteristics. In physiologic studies in transgenic mouse models modulating NPY signaling, we identified differential control of cardiac responses by these two subpopulations to high and low stress states. These findings provide novel insights into the unique properties of neurons responsible for cardiac sympathetic regulation, with implications for novel strategies to target specific neuronal subtypes for sympathetic blockade in cardiac disease.
2023-05-09 | GSE231924 | GEO
Project description:Allergic asthma develops from allergen exposure in early childhood and progresses into adulthood. The central mediator of progressive allergic asthma is allergen-specific, T helper 2 (Th2) resident memory cells (TRMs). However, whether the immature lung facilitates residence of Th2-TRMs is unknown. Employing a mouse model of progressive allergic inflammation from neonates to adults, we found that maturing sympathetic nerves enable a dopamine-enriched lung environment in early life that promotes establishment of allergen-specific Th2-TRMs. To expore the molecular mechanism, we apply bulk RNA-seq to test the transcriptome changes in mouse Th2 cells after dopamine treatment.
2023-06-01 | GSE219287 | GEO
Project description:Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.
| S-EPMC4071369 | biostudies-literature
Project description:he neural crest is an embryonic stem cell population unique to vertebrates whose expansion and diversification are thought to have promoted vertebrate evolution by enabling emergence of novel cell types and structures like jaws and peripheral ganglia2. While basal vertebrates have sensory ganglia, convention has it that trunk sympathetic chain ganglia arose only in jawed vertebrates. In contrast, here we report the presence of trunk sympathetic neurons in the sea lamprey, Petromyzon marinus, an extant jawless vertebrate. These neurons arise from sympathoblasts near the dorsal aorta that undergo noradrenergic specification via a transcriptional program homologous to that described in gnathostomes. Lamprey sympathoblasts populate the extracardiac space and extend along the length of the trunk in bilateral streams, expressing the catecholamine biosynthetic pathway enzymes tyrosine hydroxylase and dopamine -hydroxylase. CM-DiI lineage tracing analysis further confirmed that these cells derive from the trunk neural crest. RNA-seq of isolated ammocete trunk sympathoblasts revealed gene profiles characteristic of sympathetic neuron function. Our findings challenge prevailing dogma which posits that sympathetic ganglia are a gnathostome innovation, instead suggesting that a late-developing rudimentary sympathetic nervous system may have been characteristic of the earliest vertebrates.
2024-02-22 | GSE246248 | GEO