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Autonomic Neuroscience : Basic &... Jul 2015The major goals of this present study were 1) to further clarify which parasympathetic ganglion sends postganglionic fibers to the lower gingiva and lip that may be...
The major goals of this present study were 1) to further clarify which parasympathetic ganglion sends postganglionic fibers to the lower gingiva and lip that may be involved in the inflammatory processes besides the local factors; 2) to separately examine the central pathways regulating sympathetic and parasympathetic innervation; and 3) to examine the distribution of central premotor neurons on both sides. A retrogradely transported green fluorescent protein conjugated pseudorabies virus was injected into the lower gingiva and lip of intact and sympathectomized adult female rats. Some animals received virus in the adrenal medulla which receive only preganglionic sympathetic fibers to separately clarify the sympathetic nature of premotor neurons. After 72-120h of survival and perfusion, the corresponding thoracic part of the spinal cord, brainstem, hypothalamus, cervical, otic, submandibular and trigeminal ganglia were harvested. Frozen sections were investigated under a confocal microscope. Green fluorescence indicated the presence of the virus. The postganglionic sympathetic neurons related to both organs are located in the three cervical ganglia, the preganglionic neurons in the lateral horn of the spinal cord on ipsilateral side; premotor neurons were found in the ventrolateral medulla, locus ceruleus, gigantocellular and paraventricular nucleus and perifornical region in nearly the same number on both sides. The parasympathetic postganglionic neurons related to the gingiva are present in the otic and related to the lip are present in the otic and submandibular ganglia and the preganglionic neurons are in the salivatory nuclei. Third order neurons were found in the gigantocellular reticular and hypothalamic paraventricular nuclei and perifornical area.
Topics: Animals; Autonomic Pathways; Brain Stem; Cell Count; Female; Functional Laterality; Gingiva; Green Fluorescent Proteins; Herpesvirus 1, Suid; Hypothalamus; Immunohistochemistry; Lip; Microscopy, Confocal; Neuroanatomical Tract-Tracing Techniques; Neuronal Tract-Tracers; Neurons; Photomicrography; Rats, Wistar; Spinal Cord
PubMed: 25854799
DOI: 10.1016/j.autneu.2015.03.005 -
Journal of Neurophysiology Dec 2021Barrington's nucleus (Bar), which controls micturition behavior through downstream projections to the spinal cord, contains two types of projection neurons, Bar and Bar,...
Barrington's nucleus (Bar), which controls micturition behavior through downstream projections to the spinal cord, contains two types of projection neurons, Bar and Bar, that have different functions and target different spinal circuitry. Both types of neurons project to the L-S spinal intermediolateral (IML) nucleus, whereas Bar neurons also project to the dorsal commissural nucleus (DCN). To obtain more information about the spinal circuits targeted by Bar, we used patch-clamp recording in spinal slices from adult mice in combination with optogenetic stimulation of Bar terminals. Recording of opto-evoked excitatory postsynaptic currents (oEPSCs) in 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine, 4-chlorobenzenesulfonate (DiI)-labeled lumbosacral preganglionic neurons (LS-PGNs) revealed that both Bar neuronal populations make strong glutamatergic monosynaptic connections with LS-PGNs, whereas Bar neurons also elicited smaller-amplitude glutamatergic polysynaptic oEPSCs or polysynaptic opto-evoked inhibitory postsynaptic currents (oIPSCs) in some LS-PGNs. Optical stimulation of Bar and Bar terminals also elicited monosynaptic oEPSCs and polysynaptic oIPSCs in sacral DCN neurons, some of which must include interneurons projecting to either the IML or ventral horn. Application of capsaicin increased opto-evoked firing during repetitive stimulation of Bar terminals through the modulation of spontaneous postsynaptic currents in LS-PGNs. In conclusion, our experiments have provided insights into the synaptic mechanisms underlying the integration of inputs from Bar to autonomic circuitry in the lumbosacral spinal cord that may control micturition. Photostimulation of Bar or Bar axons in the adult mouse spinal cord elicits excitatory or inhibitory postsynaptic responses in multiple cell types related to the autonomic nervous system including preganglionic neurons (PGNs) in the lumbosacral intermediolateral nucleus and interneurons in the lumbosacral dorsal commissure nucleus. Integration of excitatory inputs from Bar and from visceral primary afferents in PGNs may be important in the regulation of micturition behavior.
Topics: Animals; Autonomic Fibers, Preganglionic; Autonomic Nervous System; Barrington's Nucleus; Electrophysiological Phenomena; Excitatory Postsynaptic Potentials; Female; Male; Mice; Optogenetics; Patch-Clamp Techniques; Spinal Cord
PubMed: 34731061
DOI: 10.1152/jn.00026.2021 -
Frontiers in Cellular Neuroscience 2017Functional properties of lamina X neurons in the spinal cord remain unknown despite the established role of this area for somatosensory integration, visceral...
Functional properties of lamina X neurons in the spinal cord remain unknown despite the established role of this area for somatosensory integration, visceral nociception, autonomic regulation and motoneuron output modulation. Investigations of neuronal functioning in the lamina X have been hampered by technical challenges. Here we introduce an spinal cord preparation with both dorsal and ventral roots still attached for functional studies of the lamina X neurons and their connectivity using an oblique LED illumination for resolved visualization of lamina X neurons in a thick tissue. With the elaborated approach, we demonstrate electrophysiological characteristics of lamina X neurons by their membrane properties, firing pattern discharge and fiber innervation (either afferent or efferent). The tissue preparation has been also probed using Ca imaging with fluorescent Ca dyes (membrane-impermeable or -permeable) to demonstrate the depolarization-induced changes in intracellular calcium concentration in lamina X neurons. Finally, we performed visualization of subpopulations of lamina X neurons stained by retrograde labeling with aminostilbamidine dye to identify sympathetic preganglionic and projection neurons in the lamina X. Thus, the elaborated approach provides a reliable tool for investigation of functional properties and connectivity in specific neuronal subpopulations, boosting research of lamina X of the spinal cord.
PubMed: 29163053
DOI: 10.3389/fncel.2017.00342 -
Journal of Clinical Medicine Nov 2021Spinocerebellar ataxia type 1 (SCA-ATXN1) is an autosomal dominant, neurodegenerative disease, caused by CAG repeat expansion in the ataxin-1 gene (). In isolated...
Spinocerebellar ataxia type 1 (SCA-ATXN1) is an autosomal dominant, neurodegenerative disease, caused by CAG repeat expansion in the ataxin-1 gene (). In isolated reports of patients with neurological signs [symptomatic patients (SP)], macular abnormalities have been described. However, no reports exist about macular anomalies in SCA1 subjects carrying the mutation without neurological signs [not symptomatic carriers (NSC)]. Therefore, the main aim of our work was to evaluate whether the macular functional and morphological abnormalities could be detectable in SP, genetically confirmed and with neurological signs, as well as in SCA-ATXN1-NSC, harboring pathogenic CAG expansion in In addition, we investigated whether the macular involvement could be associated or not to an impairment of RGCs and of their fibers and of the neural conduction along the visual pathways. Herein, nine SCA-ATXN1 subjects (6 SP and 3 NSC) underwent the following examinations: visual acuity and chromatic test assessments, fundus oculi (FO) examination, macular and peripapillary retinal nerve fiber layer thickness (RNFL-T) analysis by Spectral domain-Optical Coherence Tomography (Sd-OCT) acquisition, multifocal electroretinogram (mfERG), pattern reversal electroretinogram (PERG) and visual evoked potentials (VEP) recordings. In four eyes of two SP, visual acuity reduction and chromatic abnormalities were observed; in three of them FO changes associated with macular thinning and outer retinal defects were also detected. In three NSC eyes, slight FO abnormalities were associated with qualitative macular morphological changes. By contrast, abnormal mfERG responses (exclusively from foveal and parafoveal areas) were detected in all SP and NSC (18 eyes). No abnormalities of PERG values, RNFL-T, and VEP responses were found, but in one SP, presenting abnormal papillo-macular bundle neural conduction. Results from our SCA-ATXN1 cohort suggest that a macular dysfunction, detectable by mfERG recordings, may occur in the overt disorder, and unexpectedly in the stage of the disease in which there is still an absence of neurological signs. In NSC, an exclusive dysfunction of preganglionic macular elements can be observed, and this is associated with both normal RGCs function and neural conduction along the visual pathways.
PubMed: 34830553
DOI: 10.3390/jcm10225271 -
Anatomical Record (Hoboken, N.J. : 2007) Sep 2023Along with well-known data on the neurochemical mechanisms of nociceptor activation, there are still no clear data regarding changes in the cellular composition and...
Along with well-known data on the neurochemical mechanisms of nociceptor activation, there are still no clear data regarding changes in the cellular composition and morphological characteristics of spinal preganglionic neurons (SPN) after capsaicin treatment. The mechanism of capsaicin toxicity differs in developing and mature nerve cells. This study aimed to determine the number of SPN in the autonomic nuclei on spinal cord (SC) sections and their cross-sectional area, the localization, percentage, and profile area of SPN containing neuronal nitric oxide synthase (nNOS) and calbindin (CB) in the thoracic SC of rats of different ages (from birth to 1-year-old) after capsaicin treatment. Neonatal capsaicin treatment generally decreased the cross-sectional area of the SPN pericarya. However, the cross-sectional area of the CB-immunoreactive (IR) SPN increased in the central autonomic area in rats aged 10-30 days old after capsaicin treatment. The number of SPN decreased only in the central autonomic area of rats aged <20 days. The proportion of nNOS-IR neurons remained steady and did not change during development. The cross-sectional area of nNOS-IR SPN in capsaicin-treated rats was less than that in control rats. The results obtained will promote further studies on the mechanisms of sensory processing in the SC and the development of the sympathetic nervous system.
Topics: Rats; Animals; Nitric Oxide Synthase Type I; Capsaicin; Calbindins; Neurons; Sympathetic Nervous System; Spinal Cord; Autonomic Fibers, Preganglionic
PubMed: 35717590
DOI: 10.1002/ar.25012 -
Eksperimental'naia I Klinicheskaia... 2015The review contains an analysis of literature data on enhancement mechanisms of duodenum contractions arising during stimulation of the sympathetic trunk in the right... (Review)
Review
The review contains an analysis of literature data on enhancement mechanisms of duodenum contractions arising during stimulation of the sympathetic trunk in the right thoracic cavity in dogs. It is established in experiments that There are mostly enhancement, not relaxation of the organ contraction occured. In this case the stimulatory effect due to the excitation of the parasympathetic fibers is excluded. The trimeperedin inhibit the serotonin receptors of autonomic ganglia neurons stimulatory activity during the nerve stimulation. It is concluded that the sympathetic trunk contain the preganglionic serotonergic nerve fibers, whose activation leads to increased bowel contractions. Direct adipinate-serotonin administration increased the bowel contraction that confirm the preganglionic serotonergic nerve fibers presence in the sympathetic trunk. The practical significance of these studies is that the new approach to the development of pharmacological agents to stimulate the motility of the gastrointestinal tract was found. The trimeperedin may inhibit the serotoninergic nerves activity that resulted in the perioperative constipation in surgical patients. Practical recommendation to exclude trimeperedin in preparing the patient for surgery to prevent perioperative constipation is formulated.
Topics: Animals; Duodenum; Humans; Muscle Contraction; Muscle, Smooth; Promedol; Receptors, Serotonin; Serotonergic Neurons; Serotonin Antagonists; Sympathetic Nervous System
PubMed: 27249867
DOI: No ID Found -
Current Medical Science Feb 2023The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y family. Among these, P2X3 is a type of P2X receptor which is...
OBJECTIVE
The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y family. Among these, P2X3 is a type of P2X receptor which is specifically expressed on nerves, especially on pre-ganglionic sensory fibers. This study investigates whether gefapixant possesses the potential of inhibiting cardiac sympathetic hypersensitivity to protect against cardiac remodeling in the context of myocardial infarction.
METHODS
The Sprague-Dawley rats were divided randomly into three groups: sham group-myocardial infarction group, and myocardial infarction with gefapixant treatment group. Myocardial infarction was induced by left anterior descending branch ligation. The gefapixant solution was intraperitoneally injected each time per day for 7 days and the appropriate dosage of gefapixant was determined according to the results of hematoxylin-eosin (HE) staining and myocardial injury biomarkers. Conditions of cardiac function were assessed by echocardiograph and cardiac fibrosis was evaluated by Western blotting and immunofluorescence staining of collagen I and collagen III. The sympathetic innervation was detected by norepinephrine concentration (pg/mL), in-vivo electrophysiology, and typical sympathetic biomarkers. Inflammatory cell infiltration was shown from immunofluorescence staining and pro-inflammatory signaling pathway activation was checked by immunohistology, quantitative realtime PCR (qPCR) and Western blotting.
RESULTS
It was found that gefapixant injection of 10 mg/kg per day had the highest dosage-efficacy ratio. Furthermore, gefapixant treatment improved cardiac pump function as shown by increased LVEF and LVFS, and decreased LVIDd and LVIDs. The expression levels of collagen I and collagen III, and TNF-α were all decreased by P2X3 inhibition. Mechanistically, the decreased activation of nucleotide-binding and oligomerization domain-like receptors family pyrin-domain-containing 3 (NLRP3) inflammasome and subsequent cleavage of caspase-1 which modulated interleukin-1β (IL-1β) and IL-18 level in heart after gefapixant treatment were associated with the suppressed cardiac inflammation.
CONCLUSION
It is suggested that P2X3 inhibition by gefapixant ameliorates post-infarct autonomic nervous imbalance, cardiac dysfunction, and remodeling possibly via inactivating NLRP3 inflammasome.
Topics: Rats; Animals; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Rats, Sprague-Dawley; Myocardial Infarction; Collagen; Biomarkers
PubMed: 36622629
DOI: 10.1007/s11596-022-2658-5 -
Acta Neuropathologica Mar 2017Detection of α-synuclein lesions in peripheral tissues is a feature of human synucleinopathies of likely pathogenetic relevance and bearing important clinical...
Detection of α-synuclein lesions in peripheral tissues is a feature of human synucleinopathies of likely pathogenetic relevance and bearing important clinical implications. Experiments were carried out to elucidate the relationship between α-synuclein accumulation in the brain and in peripheral organs, and to identify potential pathways involved in long-distance protein transfer. Results of this in vivo study revealed a route-specific transmission of α-synuclein from the rat brain to the stomach. Following targeted midbrain overexpression of human α-synuclein, the exogenous protein was capable of reaching the gastric wall where it was accumulated into preganglionic vagal terminals. This brain-to-stomach connection likely involved intra- and inter-neuronal transfer of non-fibrillar α-synuclein that first reached the medulla oblongata, then gained access into cholinergic neurons of the dorsal motor nucleus of the vagus nerve and finally traveled via efferent fibers of these neurons contained within the vagus nerve. Data also showed a particular propensity of vagal motor neurons and efferents to accrue α-synuclein and deliver it to peripheral tissues; indeed, following its midbrain overexpression, human α-synuclein was detected within gastric nerve endings of visceromotor but not viscerosensory vagal projections. Thus, the dorsal motor nucleus of the vagus nerve represents a key relay center for central-to-peripheral α-synuclein transmission, and efferent vagal fibers may act as unique conduits for protein transfer. The presence of α-synuclein in peripheral tissues could reflect, at least in some synucleinopathy patients, an ongoing pathological process that originates within the brain and, from there, reaches distant organs innervated by motor vagal projections.
Topics: Animals; Autonomic Fibers, Preganglionic; Brain; Choline O-Acetyltransferase; Female; Gastric Mucosa; Green Fluorescent Proteins; Humans; Neurons; Nodose Ganglion; RNA, Messenger; Rats; Rats, Sprague-Dawley; Time Factors; Transduction, Genetic; Vagus Nerve; alpha-Synuclein
PubMed: 28012041
DOI: 10.1007/s00401-016-1661-y -
Science Advances Feb 2018The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered...
The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems.
Topics: Animals; Autonomic Fibers, Preganglionic; Autonomic Nervous System; Brain Stem; Fishes; Gases; Heart; Heart Rate; Hypoxia; Mammals; Neural Conduction; Respiration; Vagus Nerve
PubMed: 29507882
DOI: 10.1126/sciadv.aaq0800 -
Journal of Cardiovascular Development... Nov 2022Cardiac denervation is a serious problem in a number of patients, including patients after heart transplantation. The status of the parasympathetic ganglia after...
Cardiac denervation is a serious problem in a number of patients, including patients after heart transplantation. The status of the parasympathetic ganglia after crossing the preganglionic fibers of the vagus nerve has not been enough studied. The aim of our study was to assess the effect of physical training on the morphological parameters of the parasympathetic atrial ganglia and autonomic regulation of heart rate after right- and left-sided vagotomy in rats. Morphometric characteristics of the right atrial ganglia were evaluated using an immunohistochemical method after a study that included a three-time assessment of heart rate variability. It was found that right-sided vagotomy leads to both an increase in the volume of ganglion and autonomic dysfunction. No significant change in the number of nerve cells was found in animals with false and left-sided vagotomy while maintaining preganglionic innervation after the physical training, whereas exercises led to a decrease in the volume of nerve tissue of rats with right-sided denervation. It was also found that in animals with preserved vagal innervation, the volume of atrial ganglion tissue correlates with overall heart rate variability and a normalized parasympathetic component. Therefore, a positive effect from regular physical activity on parasympathetic regulation can be expected only if preganglionic vagal influence is preserved.
PubMed: 36421926
DOI: 10.3390/jcdd9110391