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.