GDNF induces synaptic vesicle markers in enteric neurons

Böttner, Martina; Harde, Jonas; Barrenschee, Martina; Hellwig, Ines; Vogel, Ilka; Ebsen, Michael; Wedel, Thilo

doi:10.1016/j.neures.2013.08.012

Cited by 23 publications

(28 citation statements)

References 36 publications

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“…We analyzed the mRNA expression of the t-SNARE snap-25 by RT-qPCR in cultured enteric neurons and found a dosedependent increase in snap-25 mRNA expression upon GDNF treatment. This finding completes our previous study in which gene expression levels of the v-SNARE synaptobrevin and also the v-SNARE-associated protein synaptophysin were upregulated by GDNF treatment (Böttner et al 2013b) and further strengthens the role of GDNF to promote synaptogenesis in general and neural plasticity in the ENS.…”

Section: Induction Of Snap-25 Expression By Neurotrophic Factorssupporting

confidence: 89%

“…Scale bar 1 µm in the GI tract. Since also other components of the exocytosis machinery have been demonstrated in the ENS, e.g., the v-SNARE synaptobrevin and the synaptophysin (Böttner et al 2013b;Sharrad et al 2013) or syntaxin 1 (Aguado et al 1999;Nirasawa et al 1997), it is likely that the t-SNARE SNAP-25 fulfills similar functions in the ENS as described for the CNS.…”

Section: Role Of Snap-25 In the Cns And Ensmentioning

confidence: 95%

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SNAP-25 is abundantly expressed in enteric neuronal networks and upregulated by the neurotrophic factor GDNF

Barrenschee

Böttner

Harde

et al. 2015

Histochem Cell Biol

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Control of intestinal motility requires an intact enteric neurotransmission. Synaptosomal-associated protein 25 (SNAP-25) is an essential component of the synaptic vesicle fusion machinery. The aim of the study was to investigate the localization and expression of SNAP-25 in the human intestine and cultured enteric neurons and to assess its regulation by the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF). SNAP-25 expression and distribution were analyzed in GDNF-stimulated enteric nerve cell cultures, and synaptic vesicles were evaluated by scanning and transmission electron microscopy. Human colonic specimens were processed for site-specific SNAP-25 gene expression analysis and SNAP-25 immunohistochemistry including dual-labeling with the pan-neuronal marker PGP 9.5. Additionally, gene expression levels and distributional patterns of SNAP-25 were analyzed in colonic specimens of patients with diverticular disease (DD). GDNF-treated enteric nerve cell cultures showed abundant expression of SNAP-25 and exhibited granular staining corresponding to synaptic vesicles. SNAP-25 gene expression was detected in all colonic layers and isolated myenteric ganglia. SNAP-25 co-localized with PGP 9.5 in submucosal and myenteric ganglia and intramuscular nerve fibers. In patients with DD, both SNAP-25 mRNA expression and immunoreactive profiles were decreased compared to controls. GDNF-induced growth and differentiation of cultured enteric neurons is paralleled by increased expression of SNAP-25 and formation of synaptic vesicles reflecting enhanced synaptogenesis. The expression of SNAP-25 within the human enteric nervous system and its downregulation in DD suggest an essential role in enteric neurotransmission and render SNAP-25 as a marker for impaired synaptic plasticity in enteric neuropathies underlying intestinal motility disorders.

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Section: Induction Of Snap-25 Expression By Neurotrophic Factorssupporting

confidence: 89%

Section: Role Of Snap-25 In the Cns And Ensmentioning

confidence: 95%

SNAP-25 is abundantly expressed in enteric neuronal networks and upregulated by the neurotrophic factor GDNF

Barrenschee

Böttner

Harde

et al. 2015

Histochem Cell Biol

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“…Synaptophysin is found within the submucosal and myenteric plexi, longitudinal and circular muscle and co-localizes with the pan-neuronal marker PGP9.5. 81 Therefore, co-labelling of K V 7 with synaptophysin and CGRP in human ileum and colon indicates expression within neuronal populations either extrinsically or intrinsically innervating the GI tract. Interestingly, the presence of K V 7 in the mucosa and submucosal plexus of the ileum is also suggestive of a role in chemosensing and possibly in response to inflammatory stimuli.…”

Section: Discussionmentioning

confidence: 97%

Peripheral K_V7 channels regulate visceral sensory function in mouse and human colon

et al. 2017

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BackgroundChronic visceral pain is a defining symptom of many gastrointestinal disorders. The KV7 family (KV7.1–KV7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral KV7 channels to visceral nociception.ResultsImmunohistochemical staining of mouse colon revealed labelling of KV7 subtypes (KV7.3 and KV7.5) with CGRP around intrinsic enteric neurons of the myenteric plexuses and within extrinsic sensory fibres along mesenteric blood vessels. Treatment with the KV7 opener retigabine almost completely abolished visceral afferent firing evoked by the algogen bradykinin, in agreement with significant co-expression of mRNA transcripts by single-cell qualitative real-time polymerase chain reaction for KCNQ subtypes and the B2 bradykinin receptor in retrogradely labelled extrinsic sensory neurons from the colon. Retigabine also attenuated responses to mechanical stimulation of the bowel following noxious distension (0–80 mmHg) in a concentration-dependent manner, whereas the KV7 blocker XE991 potentiated such responses. In human bowel tissues, KV7.3 and KV7.5 were expressed in neuronal varicosities co-labelled with synaptophysin and CGRP, and retigabine inhibited bradykinin-induced afferent activation in afferent recordings from human colon.ConclusionsWe show that KV7 channels contribute to the sensitivity of visceral sensory neurons to noxious chemical and mechanical stimuli in both mouse and human gut tissues. As such, peripherally restricted KV7 openers may represent a viable therapeutic modality for the treatment of gastrointestinal pathologies.

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“…Disorders of gastrointestinal motility have been associated with signaling components of GDNF in enteric neuropathies (21). In addition, GDNF contributes to synaptophysin and synaptobrevin expression and formatted neuronal varicosities, which induces functional neuronal networks (22). A previous study indicated that GDNF and brain-derived neurotrophic factor expression levels are upregulated and that cellular apoptosis is attenuated by acupuncture in the hippocampi of rats experiencing hypoxia-ischemia (23).…”

Section: Discussionmentioning

confidence: 99%

Gastric electrical stimulation improves enteric neuronal survival

Wang

Song

et al. 2017

International Journal of Molecular Medicine

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Research and clinical experience with vagotomy have confirmed that damage to the central nervous system severely affects physiological movement in the gastrointestinal system. The aim of this study was to investigate the effects of synchronized dual-pulse gastric electrical stimulation (SGES) on the apoptosis of enteric neurons and the possible pathways involved in these effects in vagotomized rats. For this purpose, Male Sprague-Dawley (SD) rats were randomized into a control group, an early subdiaphragmatic vagotomized group (ESDV group), an early subdiaphragmatic vagotomized group with short-term SGES (ESDV + SSGES group), a terminal subdiaphragmatic vagotomized group (TSDV group) and a terminal subdiaphragmatic vagotomized group with long-term SGES (TSDV + LSGES group). The expression levels of connexin 43 (Cx43), glial cell line-derived neurotrophic factor (GDNF), p-Akt, pan-Akt and PGP9.5 were assessed by RT-qPCR, western blot analysis and immunofluorescence staining. Apoptosis was determined by terminal-deoxynucleoitidyl transferase-mediated nick-end labeling (TUNEL) assay. We found that Cx43 expression was decreased in the ESDV and TSDV groups, but was significantly upregulated in the SSGES and LSGES groups. In addition, the GDNF and PGP9.5 expression levels were significantly decreased in the ESDV group compared with the control and TSDV groups and were upregulated in both the SSGES and LSGES groups. The LSGES group exhibited a clear increase in p-Akt expression compared with the TSDV group. Fewer TUNEL-positive cells were observed in the SSGES and LSGES groups than in the ESDV and TSDV groups. More TUNEL-positive cells were found in the stomach of rats subjected to subdiaphragmatic vagotomy. On the whole, our data indicate that SGES improved enteric neuronal survival, possibly through GDNF and the phosphatidylinositol 3-kinase (PI3K)/Akt pathways.

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GDNF induces synaptic vesicle markers in enteric neurons

Cited by 23 publications

References 36 publications

SNAP-25 is abundantly expressed in enteric neuronal networks and upregulated by the neurotrophic factor GDNF

SNAP-25 is abundantly expressed in enteric neuronal networks and upregulated by the neurotrophic factor GDNF

Peripheral K_V7 channels regulate visceral sensory function in mouse and human colon

Gastric electrical stimulation improves enteric neuronal survival

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GDNF induces synaptic vesicle markers in enteric neurons

Cited by 23 publications

References 36 publications

SNAP-25 is abundantly expressed in enteric neuronal networks and upregulated by the neurotrophic factor GDNF

SNAP-25 is abundantly expressed in enteric neuronal networks and upregulated by the neurotrophic factor GDNF

Peripheral KV7 channels regulate visceral sensory function in mouse and human colon

Gastric electrical stimulation improves enteric neuronal survival

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Peripheral K_V7 channels regulate visceral sensory function in mouse and human colon