A widely distributed antigen developmentally regulated in the nervous system

Development ◽  
1990 ◽  
Vol 109 (4) ◽  
pp. 743-752 ◽  
Author(s):  
O. Pourquie ◽  
M. Coltey ◽  
J.L. Thomas ◽  
N.M. Le Douarin

We have identified a glycoprotein (BEN) of 95–100 × 10(3) Mr using a monoclonal antibody. This protein is transiently expressed at the cell surface of the peripherally projecting neurons, i.e. motoneurons of the spinal cord and cranial nuclei, sensory neurons of the dorsal root and cranial sensory ganglia and sympathetic, parasympathetic and enteric neurons. In vitro cultures of dorsal root and sympathetic ganglia have shown that BEN is expressed on neurons but not on glial cells. On motor and sensory neurons, BEN first appears at the level of the cell body just after withdrawal from the cell cycle. Soon afterwards, expression of the antigen extends to the elongating axon. After a few days, BEN is no longer expressed by the motor and sensory neurons, disappearing first from the cell body and then progressively from the fibres. The loss of expression is concomitant with the onset of intense proliferation of satellite and Schwann cells. This modulated expression within the nervous system is unlike that of any surface glycoprotein so far described in vertebrates. Preliminary biochemical analysis indicates that, although it bears the adhesion-associated epitope HNK-1, BEN does not share characteristics with any previously described axonal glycoprotein. Consequently, we speculate that this glycoprotein might be a novel molecule implicated in selective adhesion phenomena, such as axonal fasciculation.

1991 ◽  
Vol 331 (1261) ◽  
pp. 259-262

In the developing vertebrate nervous system the survival of neurons becomes dependent on the supply of a neurotrophic factor from their targets when their axons reach these targets. To determine how the onset of neurotrophic factor dependency is coordinated with the arrival of axons in the target field, we have studied the growth and survival of four populations of cranial sensory neurons whose axons have markedly different distances to grow to reach their targets. Axonal growth rate both in vivo and in vitro is related to target distance; neurons with more distant targets grow faster. The onset trophic factor dependency in culture is also related to target distance; neurons with more distant targets survive longer before becoming trophic factor dependent. These data suggest that programmes of growth and survival in early neurons play an important role in coordinating the timing of trophic interactions in the developing nervous system.


IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S124
Author(s):  
Woon-Hae Kim ◽  
Hyun-Gyu Kang ◽  
Taehoon H. Kim ◽  
Yoon Jeong Mo ◽  
Yu Seon Kim ◽  
...  

Neuroscience ◽  
2008 ◽  
Vol 153 (4) ◽  
pp. 1153-1163 ◽  
Author(s):  
M. Fornaro ◽  
J.M. Lee ◽  
S. Raimondo ◽  
S. Nicolino ◽  
S. Geuna ◽  
...  

1997 ◽  
Vol 78 (2) ◽  
pp. 1180-1183 ◽  
Author(s):  
Michelle Bévengut ◽  
François Clarac ◽  
Daniel Cattaert

Bévengut, Michelle, François Clarac, and Daniel Cattaert. Antidromic modulation of a proprioceptor sensory discharge in crayfish. J. Neurophysiol. 78: 1180–1183, 1997. In the proprioceptive neurons of the coxo-basal chortotonal organ, orthodromic spikes convey the sensory information from the cell somata (located peripherally) to the central output terminals. During fictive locomotion, presynaptic depolarizations of these central terminals elicit bursts of antidromic spikes that travel back to the periphery. To determine whether the antidromic spikes modified the orthodromic activity of the sensory neurons, single identified primary afferents of the proprioceptor were recorded intracellularly and stimulated in in vitro preparations of crayfish nervous system. Depolarizing current pulses were delivered in trains whose frequency and duration were controlled to reproduce bursts of antidromic spikes similar to those elicited during fictive locomotion. According to their frequencies, these antidromic bursts reduce or suppress the orthodromic discharges in both position- and movement-sensitive neurons. They induce both a long-lasting silence and a gradual recovery after their occurrences. Neither the collision between the afferent and the efferent messages nor the release of serotonin by the sensory neurons can explain these results. We therefore conclude that antidromic bursts produce a peripheral modulation of the orthodromic activity of the sensory neurons, modifying their sensitivity by mechanisms yet unknown.


The Acrania possess an histologically complex peripheral nervous system, the atrial nervous system, lying just under the epithelium lining the atrium and covering the various organs within it. The system contains both sensory and motor components, and is especially rich in peripheral sensory cell bodies. It is in connexion with the central nervous system by way of the dorsal root nerves. Most of the motor axons entering the system pass to the cross-striated pterygial muscle flooring the atrium, others pass to the cross-striated trapezius muscles, and there is also a large ciliarymotor component, which controls the action of the lateral ciliary tracts of the gill bars. Unipolar sensory neurons are abundant upon the surface of the pterygial muscle, and are also found upon the parietal walls of the atrium. Multipolar sensory neurons are abundant upon the foregut and its diverticulum. The hindgut (outside the atrium) is more sparsely innervated, but occasional multipolar sensory neurons occur there. The multipolar neurons of the foregut and diverticulum appear to be in connexion one with another asynaptically, but their axons pass to the central nervous system. Similar sensory neurons of several types are found in the richly innervated atrio-coelomic funnels. The function of the atrial nervous system is not yet entirely understood, but it is probable that it is mainly concerned with the regulation of the feeding process, and with spawning. It is concluded that the system is not evidently homologous with the ‘sympathetic’ systems of the craniates, and that it is unwise at present to attempt to homologize the visceral nervous systems of the two groups.


2012 ◽  
Vol 117 (5) ◽  
pp. 1102-1112 ◽  
Author(s):  
Fei Dong ◽  
Wenrui Xie ◽  
Judith A. Strong ◽  
Jun-Ming Zhang

Background Inflammation of the dorsal root ganglia (DRG) may contribute to low back pain, postherpetic neuralgia, and neuropathic pain. The mineralocorticoid receptor (MR) plays a proinflammatory role in many nonrenal tissues, but its role in peripheral pain at the DRG level is not well studied. Methods Local inflammation of the L5 DRG with the immune activator zymosan rapidly leads to mechanical hypersensitivity and increased excitability of sensory neurons. Using this pain model, the authors applied the MR antagonist eplerenone locally to the inflamed DRG. Excitability of small-diameter sensory neurons was examined in acute primary culture by using patch clamp techniques. Results Local eplerenone significantly reduced the mechanical hypersensitivity and shortened its duration. The same dose was ineffective systemically. Immunohistochemical studies showed the MR was present in most neurons and rapidly translocated to the nucleus 1 day after local DRG inflammation. Activation of satellite glia (defined by expression of glial fibrillary acidic protein) in the inflamed DRG was also reduced by local eplerenone. Increased excitability of small-diameter sensory neurons 1 day after inflammation could be observed in vitro. Eplerenone applied in vitro (8-12 h) could reverse this increased excitability. Eplerenone had no effect in neurons isolated from normal, uninflamed DRG. The MR agonist aldosterone (10 nM) applied in vitro increased excitability of neurons isolated from normal DRG. Conclusions The MR may have a pronociceptive role in the DRG. Some of its effects may be mediated by neuronal MR. The MR may represent a novel therapeutic target in some pain syndromes.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Anastazja M. Gorecki ◽  
Chidozie C. Anyaegbu ◽  
Ryan S. Anderton

AbstractParkinson’s disease (PD) is an incurable, devastating disorder that is characterized by pathological protein aggregation and neurodegeneration in the substantia nigra. In recent years, growing evidence has implicated the gut environment and the gut-brain axis in the pathogenesis and progression of PD, especially in a subset of people who exhibit prodromal gastrointestinal dysfunction. Specifically, perturbations of gut homeostasis are hypothesized to contribute to α-synuclein aggregation in enteric neurons, which may spread to the brain over decades and eventually result in the characteristic central nervous system manifestations of PD, including neurodegeneration and motor impairments. However, the mechanisms linking gut disturbances and α-synuclein aggregation are still unclear. A plethora of research indicates that toll-like receptors (TLRs), especially TLR2 and TLR4, are critical mediators of gut homeostasis. Alongside their established role in innate immunity throughout the body, studies are increasingly demonstrating that TLR2 and TLR4 signalling shapes the development and function of the gut and the enteric nervous system. Notably, TLR2 and TLR4 are dysregulated in patients with PD, and may thus be central to early gut dysfunction in PD. To better understand the putative contribution of intestinal TLR2 and TLR4 dysfunction to early α-synuclein aggregation and PD, we critically discuss the role of TLR2 and TLR4 in normal gut function as well as evidence for altered TLR2 and TLR4 signalling in PD, by reviewing clinical, animal model and in vitro research. Growing evidence on the immunological aetiology of α-synuclein aggregation is also discussed, with a focus on the interactions of α-synuclein with TLR2 and TLR4. We propose a conceptual model of PD pathogenesis in which microbial dysbiosis alters the permeability of the intestinal barrier as well as TLR2 and TLR4 signalling, ultimately leading to a positive feedback loop of chronic gut dysfunction promoting α-synuclein aggregation in enteric and vagal neurons. In turn, α-synuclein aggregates may then migrate to the brain via peripheral nerves, such as the vagal nerve, to contribute to neuroinflammation and neurodegeneration typically associated with PD.


Development ◽  
1995 ◽  
Vol 121 (1) ◽  
pp. 135-147 ◽  
Author(s):  
D. Sanchez ◽  
M.D. Ganfornina ◽  
M.J. Bastiani

This article describes the expression pattern and functional analysis of Lazarillo, a novel cell surface glycoprotein expressed in the embryonic grasshopper nervous system, and a member of the lipocalin family. Lazarillo is expressed by a subset of neuroblasts, ganglion mother cells and neurons of the central nervous system, by all sensory neurons of the peripheral nervous system, and by a subset of neurons of the enteric nervous system. It is also present in a few non neuronal cells associated mainly with the excretory system. A monoclonal antibody raised against Lazarillo perturbs the extent and direction of growth of identified commissural pioneer neurons. We propose that Lazarillo is the receptor for a midline morphogen involved in the outgrowth and guidance of these neurons.


2014 ◽  
Vol 307 (8) ◽  
pp. G848-G862 ◽  
Author(s):  
Martha G. Welch ◽  
Kara G. Margolis ◽  
Zhishan Li ◽  
Michael D. Gershon

Enteric neurons express oxytocin (OT); moreover, enteric neurons and enterocytes express developmentally regulated OT receptors (OTRs). Although OT (with secretin) opposes intestinal inflammation, physiological roles played by enteric OT/OTR signaling have not previously been determined. We tested hypotheses that OT/OTR signaling contributes to enteric nervous system (ENS)-related gastrointestinal (GI) physiology. GI functions and OT effects were compared in OTR-knockout (OTRKO) and wild-type (WT) mice. Stool mass and water content were greater in OTRKO mice than in WT. GI transit time in OTRKO animals was faster than in WT; OT inhibited in vitro generation of ENS-dependent colonic migrating motor complexes in WT but not in OTRKO mice. Myenteric neurons were hyperplastic in OTRKO animals, and mucosal exposure to cholera toxin (CTX) in vitro activated Fos in more myenteric neurons in OTRKO than WT than in WT mice; OT inhibited the CTX response in WT but not in OTRKO mice. Villi and crypts were shorter in OTRKO than in WT mice, and transit-amplifying cell proliferation in OTRKO crypts was deficient. Macromolecular intestinal permeability in OTRKO was greater than WT mice, and experimental colitis was more severe in OTRKO mice; moreover, OT protected WT animals from colitis. Observations suggest that OT/OTR signaling acts as a brake on intestinal motility, decreases mucosal activation of enteric neurons, and promotes enteric neuronal development and/or survival. It also regulates proliferation of crypt cells and mucosal permeability; moreover OT/OTR signaling is protective against inflammation. Oxytocinergic signaling thus appears to play an important role in multiple GI functions that are subject to neuronal regulation.


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