The bowel and beyond: the enteric nervous system in neurological disorders

Abstract

The enteric nervous system (ENS) is large, complex and uniquely able to orchestrate gastrointestinal behaviour independently of the central nervous system (CNS). An intact ENS is essential for life and ENS dysfunction is often linked to digestive disorders. The part the ENS plays in neurological disorders, as a portal or participant, has also become increasingly evident. ENS structure and neurochemistry resemble that of the CNS, therefore pathogenic mechanisms that give rise to CNS disorders might also lead to ENS dysfunction, and nerves that interconnect the ENS and CNS can be conduits for disease spread. We review evidence for ENS dysfunction in the aetiopathogenesis of autism spectrum disorder, amyotrophic lateral sclerosis, transmissible spongiform encephalopathies, Parkinson disease and Alzheimer disease. Animal models suggest that common pathophysiological mechanisms account for the frequency of gastrointestinal comorbidity in these conditions. Moreover, the neurotropic pathogen, varicella zoster virus (VZV), unexpectedly establishes latency in enteric and other autonomic neurons that do not innervate skin. VZV reactivation in these neurons produces no rash and is therefore a clandestine cause of gastrointestinal disease, meningitis and strokes. The gut–brain alliance has raised consciousness as a contributor to health, but a gut–brain axis that contributes to disease merits equal attention.

Viruses in human central nervous system — invasion, transmission, and latency: a literature review

“…Так, РНК вирусы -вирус Западного Нила (WNV) [27], вирус гепатита С (HCV) [28], HTLV-1 [29], ДНК вирусы JCV [30], вирус Епштейна-Барр (EBV) [31], цитомегаловирус (HCMV), способны инфициро-вать микроваскулярный эпителий, что обусловли-вает нарушение целостности ГЭБ и сопровождается неконтролированной миграцией иммунных клеток в ткань мозга [32][33][34].…”

“…Вирионам не присуще распростра-нение от клетки к клетке путем свободной диффузии. Инфицированные ПНС нейроны часто находятся в прямом синаптическом контакте с нейронами ЦНС, открывая прямой путь к распространению [33]. Таким образом, инфицирование ЦНС частично определяется нейрональными транспортными системами, вдоль которых распространяются вирусы.…”

A New Perspective on Parkinson’s Disease: Pathology Begins in the Gastrointestinal Tract

“…Prior to subcortical disturbance, insoluble alpha-synuclein aggregates have been found throughout the GI tract, causing disrupted gastric motility in transgenic mice (Rao & Gershon, 2016). In the absence of central nervous system (CNS) pathology, genetic mouse models show an increased GI transit time (i.e., longer duration of ingested substance movement through the GI tract compared to the norm) with decreased colonic motility compared to controls (Rao & Gershon, 2016).…”

“…In the absence of central nervous system (CNS) pathology, genetic mouse models show an increased GI transit time (i.e., longer duration of ingested substance movement through the GI tract compared to the norm) with decreased colonic motility compared to controls (Rao & Gershon, 2016). Increased GI transit time can result in constipation (Rao & Gershon, 2016).…”

“…In the absence of central nervous system (CNS) pathology, genetic mouse models show an increased GI transit time (i.e., longer duration of ingested substance movement through the GI tract compared to the norm) with decreased colonic motility compared to controls (Rao & Gershon, 2016). Increased GI transit time can result in constipation (Rao & Gershon, 2016). Gastrointestinal deficits are some of the most prevalent non-motor symptoms in PD patients and they have shown to affect more than 65% of patients in various cultures (Bugalho et al,2016;Cheon et al, 2008).…”