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Morphology of Schwann Cell Processes Supports Renal Sympathetic Nerve Terminals With Local Distribution of Adrenoceptors.

ABSTRACT: Nerves in the renal parenchyma comprise sympathetic nerves that act on renal arteries and tubules to decrease blood flow and increase primary urine reabsorption, respectively. Synaptic vesicles release neurotransmitters that activate their effector tissues. However, the mechanisms by which neurotransmitters exert individual responses to renal effector cells remain unknown. Here, we investigated the spatial and molecular compositional associations of renal Schwann cells (SC) supporting the nerve terminals in male rats. The nerve terminals of vascular smooth muscle cells (SMCs) enclosed by renal SC processes were exposed through windows facing the effectors with presynaptic specializations. We found that the adrenergic receptors (ARs) α2A, α2C, and β2 were localized in the SMC and the basal side of the tubules, where the nerve terminals were attached, whereas the other subtypes of ARs were distributed in the glomerular and luminal side, where the norepinephrine released from nerve endings may have indirect access to ARs. In addition, integrins α4 and β1 were coexpressed in the nerve terminals. Thus, renal nerve terminals could contact their effectors via integrins and may have a structure, covered by SC processes, suitable for intensive and directional release of neurotransmitters into the blood, rather than specialized structures in the postsynaptic region.

SUBMITTER: Maeda S

PROVIDER: S-EPMC9284235 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Morphology of Schwann Cell Processes Supports Renal Sympathetic Nerve Terminals With Local Distribution of Adrenoceptors.

Maeda Seishi S Minato Yusuke Y Kuwahara-Otani Sachi S Yamanaka Hiroki H Maeda Mitsuyo M Kataoka Yosky Y Yagi Hideshi H

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20220616 7

Nerves in the renal parenchyma comprise sympathetic nerves that act on renal arteries and tubules to decrease blood flow and increase primary urine reabsorption, respectively. Synaptic vesicles release neurotransmitters that activate their effector tissues. However, the mechanisms by which neurotransmitters exert individual responses to renal effector cells remain unknown. Here, we investigated the spatial and molecular compositional associations of renal Schwann cells (SC) supporting the nerve ...[more]

PMID: 35708491

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Project description:BackgroundThe intracardiac nervous system (ICNS) is composed of neurons, in association with Schwann cells (SC) and endoneurial cardiac fibroblasts (ECF). Besides heart rhythm control, recent studies have implicated cardiac nerves in postnatal cardiac regeneration and cardiomyocyte size regulation, but cardiac SC and ECF remain understudied. During the postnatal period, the ICNS undergoes intense remodeling with nerve fasciculation and elongation throughout the myocardium, partially guided by the extracellular matrix (ECM). Here we report the origins, heterogeneity, and functions of SC and ECF that develop in proximity to neurons during postnatal ICNS maturation.Methods and resultsPeriostin lineage (Postn+) cells include cardiac Remak SC and ECF during the postnatal period in mice. The developmental origins of cardiac SC and ECF were examined using Rosa26eGFP reporter mice bred with Wnt1Cre, expressed in Neural crest (NC)-derived lineages, or tamoxifen-inducible Tcf21MerCreMer, expressed predominantly in epicardial-derived fibroblast lineages. ICNS components are NC-derived with the exceptions of the myelinating Plp1+ SC and the Tcf21+ lineage-derived intramural ventricular ECF. In addition, Postn+ lineage GFAP- Remak SC and ECF are present around the fasciculating cardiac nerves. Whole mount studies of the NC-derived cells confirmed postnatal maturation of the complex ICNS network from P0 to P30. Sympathetic, parasympathetic, and sensory neurons fasciculate from P0 to P7 indicated by co-staining with PSA-NCAM. Ablation of Postn+ cells from P0 to P6 or loss of Periostin leads to reduced fasciculation of cardiac sympathetic nerves. In addition, collagen remodeling surrounding maturing nerves of the postnatal heart is reduced in Postn-null mice.ConclusionsPostn+ cells include cardiac SC and ECF during postnatal nerve maturation, and these cells have different embryonic origins. At P7, the Postn+ cells associated with cardiac nerves are mainly Remak SC and ECF. Ablation of the Postn+ cells from P0 to P6 and also loss of Postn in Postn-null mice leads to reduced fasciculation of cardiac nerves at P7.

Project description:Prejunctional nicotinic acetylcholine receptors (nAChRs) amplify postganglionic sympathetic neurotransmission, and there are indications that intraterminal Ca(2+) stores might be involved. However, the mechanisms by which nAChR activation stimulates neurotransmitter release at such junctions is unknown. Rapid local delivery (picospritzing) of the nAChR agonist epibatidine was combined with intracellular sharp microelectrode recording to monitor spontaneous and field-stimulation-evoked neurotransmitter release from sympathetic nerve terminals in the mouse isolated vas deferens. Locally applied epibatidine (1 µM) produced 'epibatidine-induced depolarisations' (EIDs) that were similar in shape to spontaneous excitatory junction potentials (SEJPs) and were abolished by nonselective nAChR antagonists and the purinergic desensitizing agonist α,β-methylene ATP. The amplitude distribution of EIDs was only slightly shifted towards lower amplitudes by the selective α7 nAChR antagonists α-bungarotoxin and methyllcaconitine, the voltage-gated Na(+) channel blocker tetrodotoxin or by blocking voltage-gated Ca(2+) channels with Cd(2+). Lowering the extracellular Ca(2+) concentration reduced the frequency of EIDs by 69%, but more surprisingly, the Ca(2+)-induced Ca(2+) release blocker ryanodine greatly decreased the amplitude (by 41%) and the frequency of EIDs by 36%. Ryanodine had no effect on electrically-evoked neurotransmitter release, paired-pulse facilitation, SEJP frequency, SEJP amplitude or SEJP amplitude distribution. These results show that activation of non-α7 nAChRs on sympathetic postganglionic nerve terminals induces high-amplitude junctional potentials that are argued to represent multipacketed neurotransmitter release synchronized by intraterminal Ca(2+)-induced Ca(2+) release, triggered by Ca(2+) influx directly through the nAChR. This nAChR-induced neurotransmitter release can be targeted pharmacologically without affecting spontaneous or electrically-evoked neurotransmitter release.

Project description:Introduction: The cholinergic anti-inflammatory pathway (CAIP) has been proposed as an efferent neural pathway dampening the systemic inflammatory response via the spleen. The CAIP activates the splenic neural plexus and a subsequent series of intrasplenic events, which at least require a close association between sympathetic nerves and T cells. Knowledge on this pathway has mostly been derived from rodent studies and only scarce information is available on the innervation of the human spleen. This study aimed to investigate the sympathetic innervation of different structures of the human spleen, the topographical association of nerves with T cells and age-related variations in nerve distribution. Materials and Methods: Spleen samples were retrieved from a diagnostic archive and were allocated to three age groups; neonates, 10-25 and 25-70 years of age. Sympathetic nerves and T cells were identified by immunohistochemistry for tyrosine hydroxylase (TH) and the membrane marker CD3, respectively. The overall presence of sympathetic nerves and T cells was semi-automatically quantified and expressed as total area percentage. A predefined scoring system was used to analyze the distribution of nerves within different splenic structures. Results: Sympathetic nerves were observed in all spleens and their number appeared to slightly increase from birth to adulthood and to decrease afterward. Irrespective to age, more than halve of the periarteriolar lymphatic sheaths (PALSs) contained sympathetic nerves in close association with T cells. Furthermore, discrete sympathetic nerves were observed in the capsule, trabeculae and red pulp and comparable to the total amount of sympathetic nerves, showed a tendency to decrease with age. No correlation was found between the number of T cells and sympathetic nerves. Conclusion: The presence of discrete sympathetic nerves in the splenic parenchyma, capsule and trabecular of human spleens could suggest a role in functions other than vasoregulation. In the PALS, sympathetic nerves were observed to be in proximity to T cells and is suggestive for the existence of the CAIP in humans. Since sympathetic nerve distribution shows interspecies and age-related variation, and our general understanding of the relative and spatial contribution of splenic innervation in immune regulation is incomplete, it remains difficult to estimate the anti-inflammatory potential of targeting splenic nerves in patients.

Project description:ObjectiveTo study the distribution of sympathetic nerves of the ligamentum flavum (LF), confirm its existence by histological observation and nuclear magnetic resonance spectroscopy, and analyze the relationship between sympathetic nerve fibers and the biomechanical structure of the LF.MethodsRandomly controlled scientific research selected 15 cases of posterior surgery in the affiliated hospital of Qingdao University from January 2013 to December 2019. The average age was 67.5 ± 14.5 years old, eight males and seven females. The LF specimens (completely separated fresh tissue) of different segments (C3-7 ) were taken during the operation. Two pages of LF specimens on the left and right sides of the same segment are randomly allocated by the pairing method for formalin fixation and cryopreservation in liquid nitrogen. LF specimens extracted from seven other adult cadaver specimens (average age at death of about 56.8 ± 4.0 years, three males and four females) were used as a control group; together with formalin- fixed specimens obtained during surgery, 3D slices were given layer by layer. The distribution of sympathetic nerves in different parts of the LF was analyzed by glyoxylic acid-induced biological monoamine fluorescent technique (SPG) and hematoxylin-eosin (HE) staining. Fifteen liquid nitrogen storage specimens were divided into the back of the LF and the spinal canal through frozen sections, and were analyzed by nuclear magnetic resonance spectroscopy-hydrogen spectrum (1 H -NMR) for neurotransmitters and neurometabolites.ResultsThere were type C sympathetic nerve fibers in the LF, which were divided into linear shape (α) and wave shape (β). Experimental group (χ2 = 1.705, P > 0.05) and control group (χ2 = 0.879, P > 0.05) can detect no difference in fluorescence units. Nerve fiber transmitter metabolites choline (Cho), creator (Cr), γ-aminobutyric acid (GABA) also indicate that the sympathetic nerve is present in the LF. LF sympathetic nerve fibers were mainly distributed in the proximal spinal canal surface, nerve fibers on the medial belt (area II) were fewer than the lateral belt (area I) (W = 210, P < 0.05). The 1 HNMR spectrum of LF spinal canal PG / Cho (t = 8.721, P < 0.05), GABA (t = 16.01, P < 0.05) value increased, lactic acid (Lac) / Cr (t = 4.213, P < 0.05), Cho / Cr (t = 2.402, P < 0.05) value decreased, indicating that nerve fibers are actively metabolized on the surface of the spinal canal, mainly distributed in tube surface. βtype fibers were more often distributed around microvessels. A small amount of α type fibers went next to the vascular structures, while α type fibers and β type fibers go cross within LF. Two patients with vertebral artery dissection had no recurrence of sympathetic symptoms within a total of 12 follow-ups 2 years after discharge.ConclusionsThere are many sympathetic nerve fibers distributed on LF, and their distribution may be correlated with histological and mechanical characteristics of LF. It may also be the anatomical basis of cervical vertigo.

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Morphology of Schwann Cell Processes Supports Renal Sympathetic Nerve Terminals With Local Distribution of Adrenoceptors.

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Morphology of Schwann Cell Processes Supports Renal Sympathetic Nerve Terminals With Local Distribution of Adrenoceptors.

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