Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer’s disease

Abstract Alzheimer’s disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is noteworthy since cortical and hypothalamic somatostatin content is reduced in neurodegenerative pathologies. Yet a possible role of a somatostatin signal deficit in the maintenance of noradrenergic projections remains unknown. Here, we deployed tissue microarrays, immunohistochemistry, quantitative morphometry and mRNA profiling in a cohort of Alzheimer’s and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer’s disease, we found significantly reduced somatostatin protein expression in the temporal cortex, with aberrant clustering and bulging of tyrosine hydroxylase-immunoreactive afferents. As such, somatostatin receptor 2 (SSTR2) mRNA was highly expressed in the human LC, with its levels significantly decreasing from Braak stages III/IV and onwards, i.e., a process preceding advanced Alzheimer’s pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine β-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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ConclusionTargeted ablation of TRPV-1/TH positive sympathetic neurons induced by RTX stellate microinjection could suppress ischemia-induced cardiac autonomic imbalances and cardiac electrophysiology instability to protect against AMI-induced VAs.
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
CONCLUSION: Targeted ablation of TRPV-1/TH positive sympathetic neurons induced by RTX stellate microinjection could suppress ischemia-induced cardiac autonomic imbalances and cardiac electrophysiology instability to protect against AMI-induced VAs. PMID: 31600641 [PubMed - as supplied by publisher]
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
Abstract P2X3 is a ligand-gated nonselective cation channel and permeable to Na+, K+ and Ca2+. Adenosine triphosphate (ATP) activation of the P2X3 on primary sensory ganglion neurons is involved in nociceptive transmission. Puerarin is a major active ingredient extracted from the traditional Chinese medicine Ge-gen. Puerarin inhibits nociceptive signal transmission by inhibiting the P2X3 in the dorsal root ganglia (DRG) and sympathetic ganglia, but its molecular mechanism is unclear. The aim of this study was to explore the molecular mechanism of puerarin on the P2X3. Here, molecular docking results revealed that ...
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Tags: Int J Biol Macromol Source Type: research
We present a novel case of a child with drug-refractory VT storm and prolonged QT requiring extracorporeal membrane oxygenation (ECMO) support. Continuous stellate ganglion blockade was remarkably effective in stabilizing his rhythm and should be considered in similar pediatric cases.
Source: A&A Case Reports - Category: Anesthesiology Tags: Case Reports Source Type: research
PURPOSE OF REVIEW The goal of this article is to review the anatomy and physiology of pupillary function and then employ that information to develop a comprehensive framework for understanding and diagnosing pupillary disorders. RECENT FINDINGS The contribution of rods and cones to the pupillary light reflex has long been known. A third photosensitive cell type, the intrinsically photosensitive retinal ganglion cell, has recently been discovered. This cell type employs melanopsin to mediate a portion of the pupillary light reflex independent of rods and cones (the postillumination pupillary response) and photic regula...
Source: CONTINUUM: Lifelong Learning in Neurology - Category: Neurology Tags: REVIEW ARTICLES Source Type: research
Action potential-induced vesicular exocytosis is considered exclusively Ca2+ dependent in Katz’s Ca2+ hypothesis on synaptic transmission. This long-standing concept gets an exception following the discovery of Ca2+-independent but voltage-dependent secretion (CiVDS) and its molecular mechanisms in dorsal root ganglion sensory neurons. However, whether CiVDS presents only in sensory cells remains...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus Source Type: research
We report the case of a 65-year-old man brought in by ambulance who complained of chest pain and received an out-of-hospital ECG suggestive of anterior-wall ST-segment elevation myocardial infarction. Shortly after arrival, the patient became unresponsive, with no palpable pulse, and was found to be in ventricular fibrillation. The patient’s ventricular fibrillation persisted despite repeated attempts at standard and double sequential defibrillation, multiple rounds of epinephrine, and amiodarone, magnesium, and bicarbonate. After these interventions were exhausted, a stellate ganglion blockade was conducted after an...
Source: Annals of Emergency Medicine - Category: Emergency Medicine Source Type: research
Abstract In this work, we investigated changes in the morphology of intrinsically photosensitive retinal ganglion cells (ipRGCs), M1 subtype, and pupillary light reflex following local and selective ablation of photoreceptors in mice. Laser photocoagulation was used to selectively destroy four patches of photoreceptors per eye at around 4 papillary diameters from the optic disc and at the 3, 6, 9, and 12 o'clock positions between the retinal vessels in the adult mouse retina, leaving cells in the inner retina intact. Morphological parameters of individual M1 cells specifically labeled by the antibody against melan...
Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research
AbstractBackgroundThe discussions at the surgical levels (sympathectomy levels) about endoscopic thoracic sympathectomy (ETS) method, which is applied in hyperhidrosis treatment in the present day and acknowledged as the golden treatment method, continue. Mainly, most of the studies evaluates postoperative early period results. Our aim in this study is to compare the long-term quality of life depending on the different surgical levels (sympathectomy levels) and evaluate the postoperative complications.Methods165 patients operated due to palmar hyperhidrosis between January 2012 and July 2017 were evaluated. Sympathectomy w...
Source: General Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Abstract Background: Aberrant afferent signaling drives adverse remodeling of the cardiac nervous system in ischemic heart disease. The study objective was to determine whether thoracic spinal dorsal column stimulation (SCS) modulates cardiac afferent sensory transduction of the ischemic ventricle. Methods: In anesthetized canines (n=16), extracellular activity generated by 62 dorsal root ganglia soma (T1-T3), with verified myocardial ischemic (MI) sensitivity, were evaluated with and without 20 min pre-emptive SCS (T1-T3 spinal level; 50 Hz, 90% motor threshold). Transient MI was induced by 1 min coronary artery ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research
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