scholarly journals Satellite glia are essential modulators of sympathetic neuron survival, activity, and autonomic function

2021 ◽  
Author(s):  
Aurelia Mapps ◽  
Erica Boehm ◽  
Corinne Beier ◽  
William Thomas Keenan ◽  
Jennifer Langel ◽  
...  

Satellite glia are the major glial cells in sympathetic ganglia, enveloping neuronal cell bodies. Despite this intimate association, how satellite glia contribute to sympathetic functions remain unclear. Here, we show that satellite glia are critical for metabolism, survival, and activity of sympathetic neurons and modulate autonomic behaviors in mice. Adult ablation of satellite glia results in impaired mTOR signaling, soma atrophy, reduced noradrenergic enzymes, and loss of sympathetic neurons. However, persisting neurons have elevated activity, and satellite glia-ablated mice show increased pupil dilation and heart rate, indicative of enhanced sympathetic tone. Satellite glia-specific deletion of Kir4.1, an inward-rectifying potassium channel, largely recapitulates the cellular defects observed in glia-ablated mice, suggesting that satellite glia act in part via extracellular K+ buffering. These findings highlight neuron-satellite glia as functional units in regulating sympathetic output, with implications for disorders linked to sympathetic hyper-activity such as cardiovascular disease and hypertension.

2019 ◽  
Author(s):  
Joana Enes ◽  
Surbhi Sona ◽  
Nega Gerard ◽  
Alexander C. Mitchell ◽  
Marian Haburcak ◽  
...  

AbstractPostganglionic sympathetic neurons and satellite glial cells are the two major cell types of the peripheral sympathetic ganglia. Sympathetic neurons project to and provide neural control of peripheral organs and have been implicated in human disorders ranging from cardiovascular disease to peripheral neuropathies. Here we show that satellite glia regulate postnatal development and activity of sympathetic neurons, providing evidence for local ganglionic control of sympathetic drive. We show changes in the cellular architecture of the rat sympathetic ganglia during the postnatal period, with satellite glia enwrapping sympathetic neuronal somata during a period of neuronal hypertrophy. In culture, satellite glia contribute to neuronal survival, promote synapse formation and play a modulatory role in neuron-to-neuron cholinergic neurotransmission, consistent with the close contact seen within the ganglia. Cultured satellite glia make and release neurotrophins, which can partially rescue the neurons from nerve growth factor deprivation. Electrophysiological recordings and immunocytochemical analysis on cultured sympathetic neurons show that satellite glial cells influence synapse number and total neuronal activity with little effect on neuronal intrinsic excitability. Thus, satellite glia play an early and ongoing role within the postnatal sympathetic ganglia, expanding our understanding of the contributions of local and target-derived factors in the regulation of sympathetic neuron function.


1997 ◽  
Vol 110 (18) ◽  
pp. 2165-2173
Author(s):  
M.J. McCarthy ◽  
L.L. Rubin ◽  
K.L. Philpott

In order to study the involvement of caspases in neuronal cell death, we have examined the effects of the viral caspase inhibitor p35 and peptide caspase inhibitors on sympathetic neurons isolated from the superior cervical ganglion (SCG). In these neurons, apoptosis can be induced by the withdrawal of nerve growth factor (NGF) and also by the addition of the kinase inhibitor staurosporine. p35 has been shown to be a broad spectrum inhibitor of the caspase family and promotes the survival of SCG neurons withdrawn from NGF. We show that p35 is also protective when apoptosis is induced by staurosporine. In addition, p35 inhibits a number of the morphological features associated with apoptosis, such as nuclear condensation, TUNEL labelling, and externalisation of phosphatidylserine. The tri-peptide caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp (O-methyl)-fluoromethylketone (zVAD-fmk) was effective at inhibiting NGF withdrawal-induced and staurosporine-induced apoptosis of SCG neurons. Two other peptide inhibitors, acetyl-Tyr-Val-Ala-Asp-aldehyde (Ac-YVAD-CHO) and acetyl-Asp-Glu-Ala-Asp-aldehyde (Ac-DEVD-CHO), also inhibited apoptosis induced by both means when microinjected into SCG neurons but peptides derived from the caspase cleavage site in p35 were not protective. We present data to suggest that apoptosis induced by separate death stimuli can result either in the activation of distinct caspases or in differences in the time of activation of the family members.


2004 ◽  
Vol 92 (5) ◽  
pp. 2659-2671 ◽  
Author(s):  
Diek W. Wheeler ◽  
Paul H. M. Kullmann ◽  
John P. Horn

Biological gain mechanisms regulate the sensitivity and dynamics of signaling pathways at the systemic, cellular, and molecular levels. In the sympathetic nervous system, gain in sensory-motor feedback loops is essential for homeostatic regulation of blood pressure and body temperature. This study shows how synaptic convergence and plasticity can interact to generate synaptic gain in autonomic ganglia and thereby enhance homeostatic control. Using a conductance-based computational model of an idealized sympathetic neuron, we simulated the postganglionic response to noisy patterns of presynaptic activity and found that a threefold amplification in postsynaptic spike output can arise in ganglia, depending on the number and strength of nicotinic synapses, the presynaptic firing rate, the extent of presynaptic facilitation, and the expression of muscarinic and peptidergic excitation. The simulations also showed that postsynaptic refractory periods serve to limit synaptic gain and alter postsynaptic spike timing. Synaptic gain was measured by stimulating dissociated bullfrog sympathetic neurons with 1–10 virtual synapses using a dynamic clamp. As in simulations, the threshold synaptic conductance for nicotinic excitation of firing was typically 10–15 nS, and synaptic gain increased with higher levels of nicotinic convergence. Unlike the model, gain in neurons sometimes declined during stimulation. This postsynaptic effect was partially blocked by 10 μM Cd2+, which inhibits voltage-dependent calcium currents. These results support a general model in which the circuit variations observed in parasympathetic and sympathetic ganglia, as well as other neural relays, can enable functional subsets of neurons to behave either as 1:1 relays, variable amplifiers, or switches.


Development ◽  
2000 ◽  
Vol 127 (18) ◽  
pp. 4073-4081 ◽  
Author(s):  
M.J. Howard ◽  
M. Stanke ◽  
C. Schneider ◽  
X. Wu ◽  
H. Rohrer

The dHAND basic helix-loop-helix transcription factor is expressed in neurons of sympathetic ganglia and has previously been shown to induce the differentiation of catecholaminergic neurons in avian neural crest cultures. We now demonstrate that dHAND expression is sufficient to elicit the generation of ectopic sympathetic neurons in vivo. The expression of the dHAND gene is controlled by bone morphogenetic proteins (BMPs), as suggested by BMP4 overexpression in vivo and in vitro, and by noggin-mediated inhibition of BMP function in vivo. The timing of dHAND expression in sympathetic ganglion primordia, together with the induction of dHAND expression in response to Phox2b implicate a role for dHAND as transcriptional regulator downstream of Phox2b in BMP-induced sympathetic neuron differentiation.


Author(s):  
E. B. Masurovsky ◽  
H. H. Benitez ◽  
M. R. Murray

Recent light- and electron microscope studies concerned with the effects of D2O on the development of chick sympathetic ganglia in long-term, organized culture revealed the presence of rod-like fibrillar formations, and associated granulofibrillar bodies, in the nuclei of control and deuterated neurons. Similar fibrillar formations have been reported in the nuclei of certain mammalian CNS neurons; however, related granulofibrillar bodies have not been previously described. Both kinds of intranuclear structures are observed in cultures fixed either in veronal acetate-buffered 2%OsO4 (pH 7. 4), or in 3.5% glutaraldehyde followed by post-osmication. Thin sections from such Epon-embedded cultures were stained with ethanolic uranyl acetate and basic lead citrate for viewing in the electron microscope.


Author(s):  
Anthony A. Paparo ◽  
Judith A. Murphy

The purpose of this study was to localize the red neuronal pigment in Mytilus edulis and examine its role in the control of lateral ciliary activity in the gill. The visceral ganglia (Vg) in the central nervous system show an over al red pigmentation. Most red pigments examined in squash preps and cryostat sec tions were localized in the neuronal cell bodies and proximal axon regions. Unstained cryostat sections showed highly localized patches of this pigment scattered throughout the cells in the form of dense granular masses about 5-7 um in diameter, with the individual granules ranging from 0.6-1.3 um in diame ter. Tissue stained with Gomori's method for Fe showed bright blue granular masses of about the same size and structure as previously seen in unstained cryostat sections.Thick section microanalysis (Fig.l) confirmed both the localization and presence of Fe in the nerve cell. These nerve cells of the Vg share with other pigmented photosensitive cells the common cytostructural feature of localization of absorbing molecules in intracellular organelles where they are tightly ordered in fine substructures.


1992 ◽  
Vol 106 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Kuniyoshi Tsuda ◽  
Takemoto Shin ◽  
Sadahiko Masuko

To study the mechanism of autonomic regulation in the larynx, intralaryngeal local ganglia of the cat were investigated using immunohistochemical techniques. Small intralaryngeal ganglia were found in the peripheral portions of internal branches of the superior laryngeal nerve. Ninety-one percent of the ganglionic neurons were immunoreactive (IR) to vasoactive intestinal polypeptide (VIP), and 10% of the VIP-IR cells were also immunoreactive to enkephalin (ENK) and/or substance P (SP). The immunoreactivity of neuronal cell bodies remained unchanged even after denervation of the bilateral superior and recurrent laryngeal nerves. A dense distribution of calcitonin gene-related peptide (CGRP)-IR nerve fibers was found around almost all neuronal cells in the intralaryngeal. ganglia. A few VIP-IR, ENK-IR, and SP-IR nerve fibers were also observed. Only the CGRP-IR fibers disappeared after the denervation experiments. in the laryngeal glands and mucosal arterioles, VIP-IR nerve terminals were found that were also immunoreactive to ENK and/or SP. However, these Immunoreactive nerve endings in the glands and arterioles remained after the denervation experiments. The results of our study indicate that laryngeal exocrine secretion and blood flow are regulated by postganglionic autonomic parasympathetic fibers from intralaryngeal ganglia that contain VIP alone or VIP with ENK and/or SP, and that these ganglionic neurons may be innervated by CGRP-IR extrinsic nerve fibers.


1991 ◽  
Vol 115 (2) ◽  
pp. 461-471 ◽  
Author(s):  
A Batistatou ◽  
L A Greene

Past studies have shown that serum-free cultures of PC12 cells are a useful model system for studying the neuronal cell death which occurs after neurotrophic factor deprivation. In this experimental paradigm, nerve growth factor (NGF) rescues the cells from death. It is reported here that serum-deprived PC12 cells manifest an endonuclease activity that leads to internucleosomal cleavage of their cellular DNA. This activity is detected within 3 h of serum withdrawal and several hours before any morphological sign of cell degeneration or death. NGF and serum, which promote survival of the cells, inhibit the DNA fragmentation. Aurintricarboxylic acid (ATA), a general inhibitor of nucleases in vitro, suppresses the endonuclease activity and promotes long-term survival of PC12 cells in serum-free cultures. This effect appears to be independent of macromolecular synthesis. In addition, ATA promotes long-term survival of cultured sympathetic neurons after NGF withdrawal. ATA neither promotes nor maintains neurite outgrowth. It is hypothesized that the activation of an endogenous endonuclease could be responsible for neuronal cell death after neurotrophic factor deprivation and that growth factors could promote survival by leading to inhibition of constitutively present endonucleases.


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