Myenteric expression of nerve growth factor and the p75 neurotrophin receptor regulate axonal remodeling as a consequence of colonic inflammation in mice

Petrie, Casey; Armitage, Michael N.; Kawaja, Michael D.

doi:10.1016/j.expneurol.2015.06.010

Cited by 10 publications

(8 citation statements)

References 53 publications

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“…Data accumulated during the last years suggest that neurotrophic factors (NTFs), including nerve growth factor (NGF) and the family of glial cell line–derived NTFs (GDNF, artemin, and neurturin), are implicated in the sensorial alterations observed in inflammatory and functional gastrointestinal disorders. Evidence obtained from animal models of IBS and gut inflammation show an up‐regulation in NTF expression, suggesting their implication in the sensitization of enteric afferent neurons . For instance, knockout mice for the GDNF family receptor α 3 (GDNF α 3), a component of the receptor of the growth factor artemin, showed reduced visceral pain‐related respon‐ses during TNBS‐induced colitis, in agreement with observations in vitro showing that colorectal afferents from these mice failed to sensitize when exposed to inflammatory mediators .…”

Section: Introductionsupporting

confidence: 74%

“…Evidence obtained from animal models of IBS and gut inflammation show an up-regulation in NTF expression, suggesting their implication in the sensitization of enteric afferent neurons. [6][7][8] For instance, knockout mice for the GDNF family receptor a 3 (GDNFa 3), a component of the receptor of the growth factor artemin, showed reduced visceral pain-related responses during TNBS-induced colitis, in agreement with observations in vitro showing that colorectal afferents from these mice failed to sensitize when exposed to inflammatory mediators. 9 Moreover, a recent study in IBS patients showed a positive correlation between abdominal pain and content of brain-derived NTF in the colonic mucosa, thus further supporting a role for NTFs in the sensitization of visceral afferents.…”

Section: Introductionsupporting

confidence: 66%

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Persistent alterations in colonic afferent innervation in a rat model of postinfectious gut dysfunction: Role for changes in peripheral neurotrophic factors

Jardí

Fernández-Blanco

Martı́nez

et al. 2016

Neurogastroenterology Motil

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Section: Introductionsupporting

confidence: 74%

Section: Introductionsupporting

confidence: 66%

Persistent alterations in colonic afferent innervation in a rat model of postinfectious gut dysfunction: Role for changes in peripheral neurotrophic factors

Jardí

Fernández-Blanco

Martı́nez

et al. 2016

Neurogastroenterology Motil

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“…As in the bladder, NGF is present in the epithelial lining of the colon [22] but recent studies show that it is produced by calretinin-positive myenteric neurons in the murine colon [95]. In colonic biopsies obtained from IBS patients, NGF levels are upregulated [96][97][98] and in rodents, NGF was similarly increased following experimental colitis [99][100][101][102][103].…”

Section: Ngf In the Colonmentioning

confidence: 99%

Partners in Crime: NGF and BDNF in Visceral Dysfunction

Coelho

Oliveira

Antunes-Lopes

et al. 2019

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: Neurotrophins (NTs), particularly Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), have attracted increasing attention in the context of visceral function for some years. Here, we examined the current literature and presented a thorough review of the subject. : After initial studies linking of NGF to cystitis, it is now well-established that this neurotrophin (NT) is a key modulator of bladder pathologies, including Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) and Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS. NGF is upregulated in bladder tissue and its blockade results in major improvements on urodynamic parameters and pain. Further studies expanded showed that NGF is also an intervenient in other visceral dysfunctions such as endometriosis and Irritable Bowel Syndrome (IBS). : More recently, BDNF was also shown to play an important role in the same visceral dysfunctions, suggesting that both NTs are determinant factors in visceral pathophysiological mechanisms. Manipulation of NGF and BDNF improves visceral function and reduce pain, suggesting that clinical modulation of these NTs may be important; however, much is still to be investigated before this step is taken. : Another active area of research is centered on urinary NGF and BDNF. Several studies show that both NTs can be found in the urine of patients with visceral dysfunction in much higher concentration than in healthy individuals, suggesting that they could be used as potential biomarkers. However, there are still technical difficulties to be overcome, including the lack of a large multicentre placebo-controlled studies to prove the relevance of urinary NTs as clinical biomarkers.

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“…No cólon, o NGF é produzido sobretudo no epitélio e por neurónios do plexo mioentérico 24,92 . O NGF participa no desenvolvimento e funcionamento do sistema nervoso entérico 93 e, como tal, alterações na sua expressão estão na origem de alterações na integridade da mucosa e no desenvolvimento de hipersensibilidade visceral, caraterísticas comuns em algumas patologias gastrointestinais.…”

Section: Fator De Crescimento Neuronal No Cólonunclassified

“…Trabalhos em modelos animais com inflamação colónica induzida por TNBS demonstraram que a expressão desta NT está aumentada na mucosa, e que a expressão e ativação do TrkB está aumentada nos aferentes sensitivos lombossagrados que enervam o cólon, seja nas projeções centrais ou nos prolongamentos axonais que correm na parede do cólon 92,96,99,102,177 . A expressão de BDNF está também aumentada no corpo celular daqueles aferentes, assumindo-se que este aumento resulta da ativação da via de sinalização ERK5, induzida pela captação e migração retrógrada de NGF a partir da mucosa colónica 101,175 .…”

Section: Fator Neurotrófico Derivado Do Cérebro No Cólonunclassified

As neurotrofinas e a dor visceral: o caso particular do fator de crescimento neuronal e do fator neurotr�fico derivado do c�rebro

Ferreira¹,

Coelho²,

Duarte-Cruz³

2021

DOR

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Neutrophins (NTs), particularly the nerve growth factor (NGF) and the brain derived neurotrophic factor (BDNF), have been attracting particular attention in the context of visceral function. In this work, we examine the current literature and present an embracing vision about the synthesis of these proteins in peripheric systems, as well as their role in the development of the most common visceral pain syndromes. After initial studies linking NGF to IC (interstitial cystitis/bladder pain syndrome), a lot of research has been done about NGF and its role in the development of urinary tract pathologies. In fact, it is now widely accepted that NGF is also a player in other visceral conditions such as CP/CPPS (chronic prostatitis/chronic pelvic pain syndrome) or IBS (irritable bowel syndrome). More recently, BDNF was also proved to play an important role in the same visceral dysfunctions, suggesting that both NTs are determinant factors in visceral pathophysiological mechanisms. While manipulation of NGF and BDNF improves visceral function and reduce pain, suggesting that clinical modulation of these NTs may be important, much is still to be investigated before this step is taken. Another important field of research has been focused on the urinary NGF and BDNF and its use as biomarkers. Several studies have showed that both NTs are present in much higher concentrations in the urine of patients with visceral dysfunctions than in healthy patients, pinpointing to the possible use of these urinary NTs as diagnosis biomarkers. Nevertheless, there are still non-answered scientific questions and technical difficulties that need to be overcome in order to fully understand the real relevance of the urinary NTs as possible clinical biomarkers.

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Myenteric expression of nerve growth factor and the p75 neurotrophin receptor regulate axonal remodeling as a consequence of colonic inflammation in mice

Cited by 10 publications

References 53 publications

Persistent alterations in colonic afferent innervation in a rat model of postinfectious gut dysfunction: Role for changes in peripheral neurotrophic factors

Persistent alterations in colonic afferent innervation in a rat model of postinfectious gut dysfunction: Role for changes in peripheral neurotrophic factors

Partners in Crime: NGF and BDNF in Visceral Dysfunction

As neurotrofinas e a dor visceral: o caso particular do fator de crescimento neuronal e do fator neurotr�fico derivado do c�rebro

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