Intestinal epithelial barrier and neuromuscular compartment in health and disease

Table 3 Summary of current human and experimental data on molecular, morphological and functional changes in intestinal epithelial barrier and neuromuscular compartment in central nervous system disorders

Central nervous system disorder	Morphofunctional changes in intestinal epithelial barrier	Morphofunctional changes in enteric neuromuscular compartment	Ref.
Human investigations
PD	↑ Intestinal permeability	↑ EGC density	[7,98-100]
	↓ Occludin and ZO-1 expression	α-syn accumulation in myenteric neurons
AD	NA	↑ Aβ, AβPP and p-Tau immunoreactivity in colonic myenteric and submucosal neurons	[102]
MS	↑ Intestinal permeability (urinary mannitol concentration)	ENS fiber disgregation	[8,101]
		EGC activation
ASD	Altered intestinal permeability	NA	[9]
Experimental models
Rotenone-induced central dopaminergic neurodegeneration	↑ Intestinal permeability	α-syn accumulation in myenteric neurons	[7,104]
		Delayed bowel transit
LPS-induced central dopaminergic neurodegeneration	↑ intestinal permeability (lactulose/mannitol ratio and sucralose levels)	α-syn accumulation in myenteric neurons	[7,104]
		Delayed bowel transit
6-OHDA-induced nigrostriatal neurodegeneration	NA	Impairment of colonic cholinergic and tachykininergic motor activity	[105-106]
Tg A53T mice (genetic model of PD)	NA	Impairment of colonic cholinergic motor activity	[107]
		α-syn accumulation in myenteric and submucosal neurons
APP/PS1 mouse (genetic model of AD)	NA	↑ Aβ protein precursor, Aβ	[4]
		Protein and p-Tau
		↓ nNOS and ChAT
		EGC activation
Tg CRND8 mice (genetic models of AD)	NA	↑ Aβ protein precursor in myenteric neurons	[4]
		Enteric glial activation (GFAP, nestin)
		Enteric neuronal loss
		Smooth muscle cell atrophy
EAE (animal model of MS)	Abnormal intestinal permeability (plasma Na-F and FITC levels)	Crypt depth and thickness of submucosal and muscular layers	[4]
	↓ ZO-1 expression	Enteric glial activation
		Neuronal loss
		Abnormal GI motility
G93A mice (genetic model of ALS)	↑ Circulating LPS	NA	[4,103]
	↓ ZO-1 and E-cadherin expression
	↑ Paneth cells number

↑: Increase; ↓: Decrease; 6-OHDA: 6-hydroxydopamine; α-syn: α-synuclein; Aβ: Amyloid β; AβPP: β-amyloid protein precursor; AD: Alzheimer’s disease; ALS: Amyotrophic lateral sclerosis; ASD: Autism spectrum disorder; ChAT: Choline acetyltransferase; EGC: Enteric glial cell; ENS: Enteric nervous system; FITC: Fluorescein isothiocyanate; GFAP: Glial fibrillary acidic protein; GI: Gastrointestinal; LPS: Lipopolysaccharide; nNOS: Neuronal nitric oxide synthase; MS: Multiple sclerosis; NA: Not available; PD: Parkinson’s disease; p-Tau: Phosphorylated Tau; ZO-1: Zonulin.