Enteric nervous system manifestations of neurodegenerative disease

Abstract

Neurological disorders cause gastrointestinal (GI) symptoms that are debilitating and markedly diminish quality of life in patients. The enteric nervous system (ENS), the intrinsic nervous system of the GI tract that is often referred to as "the second brain", shares many features with the central nervous system. The ENS plays an essential role in regulating many GI functions including motility and fluid secretion. Enteric neuronal degeneration could therefore be responsible for the GI symptoms commonly observed in neurological conditions. Here we describe the organization and functions of the ENS and then review the evidence for ENS involvement in two common neurodegenerative disorders, Parkinson's disease (PD) and Alzheimer's disease (AD). Data from patients as well as animal models suggest that PD affects distinct subsets of neurons and glia in the ENS, and that the ENS may participate in the pathogenesis of this disorder. While there has been great enthusiasm for the possibility of sampling the ENS for diagnosis or therapeutic monitoring of PD, further work is needed to determine which enteric neurons are most affected and how ENS function could be modulated to ameliorate GI symptoms in patients. Although AD is far more common than PD and AD patients also experience GI symptoms, understanding of ENS dysfunction in AD is in its infancy. Much work remains to be done in both of these fields to determine how the ENS contributes to and/or is altered by these disorders, and how to target the ENS for more effective treatment of GI comorbidities.

Brain-Gut-Microbiota Axis in Alzheimer’s Disease

“…The APP transgenic mice develop accumulation of Aβ in the enteric neurons leading to a decrease in enteric neuron abundance, dysmotility, and increased vulnerability to inflammation. 20 Preliminary data confirm that changes in the ENS in APP overexpressing transgenic mice correlate with the disease expression. 22…”

“…This connection also allows for the disease spreading. 20 In Parkinson's disease (PD) gastrointestinal dysfunction is present in almost 80% of the patients, preceding motor dysfunction. In fact, α-synucleinopathy of the ENS has been suggested to be an early indicator of PD pathology.…”

Mitochondria-mitochondria interaction networks show altered topological patterns in Parkinson’s disease

“…2a). These results may explain why PD patients have dysfunctional ganglia neurons 25 . The observed lower network efficiency and accordingly increased ASPL in MINs might have important implications, i.e., energy and information within enteric ganglia neurons are possibly produced, shared and distributed less competently in the ganglia neurons of PD patients relative to healthy controls.…”

Can oral health and oral‐derived biospecimens predict progression of dementia?

“…The gut microbiome's role in AD pathogenesis likely stems from the gut–brain axis, a bi‐directional communication pathway between the enteric and central nervous systems. Dysbiosis seen in the gut can also lead to increased expression of amyloid precursor protein in mice, which can increase an individual's risk for neuroinflammation (Chalazonitis & Rao, ). One prior study found that patients with AD had a higher abundance of gut Bacteroidetes and decreased abundance of Actinobacteria (Vogt et al, ).…”