Enteric glial cell reactivity in colonic layers and mucosal modulation in a mouse model of Parkinson’s disease induced by 6-hydroxydopamine

• Published in: Brain research bulletin Vol. 187; pp. 111 - 121
• Main Authors: Thomasi, Beatriz Bastos de Moraes, Valdetaro, Luisa, Ricciardi, Maria Carolina Garcia, Hayashide, Lívia, Fernandes, Ana Carolina Moraes Neves, Mussauer, Amanda, da Silva, Mayara Lídia, da Cunha Faria-Melibeu, Adriana, Ribeiro, Manuel Gustavo Leitão, de Mattos Coelho-Aguiar, Juliana, Campello-Costa, Paula, Moura-Neto, Vivaldo, Tavares-Gomes, Ana Lúcia
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2022; Elsevier
• Subjects: Enteric glia; Gut-brain axis; Inflammation; Intestinal epithelial barrier; Parkinson’s disease model; H&E; Gut-brain axis; IEB; 6-OHDA; Inflammation; ENS; IBA1; GFAP; Enteric glia; EGCs; GIT; GDNF; PD; TH; TNF-α; Parkinson’s disease model; CTTF; Intestinal epithelial barrier
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2022.06.013

Enteric glial cells (EGCs) constitute the majority of the neural population of the enteric nervous system and are found in all layers of the gastrointestinal tract. It is active in enteric functions such as immunomodulation, participating in inflammation and intestinal epithelial barrier (IEB) regulation. Both EGCs and IEB have been described as altered in Parkinson's disease (PD). Using an animal model of PD induced by 6-hydroxydopamine (6-OHDA), we investigated the effect of ongoing neurodegeneration on EGCs and inflammatory response during short periods after model induction. C57Bl/6 male mice were unilaterally injected with 6-OHDA in the striatum. Compared to the control group, 6-OHDA animals showed decreased relative water content in their feces from 1 w after model induction. Moreover, at 1 and 2 w post-induction, groups showed histopathological changes indicative of intestinal inflammation. We identified an increase in IBA1 and GFAP levels in the intestinal mucosa. At an earlier survival of 48 h, we detected an increase in GFAP in the neuromuscular layer, suggesting that it was a primary event for the upregulation of GDNF, TNF-α, and occludin in the intestinal mucosa observed after 1 w. Within 2 w, we identified a decrease in the expression of occludin barrier proteins. Thus, EGCs modulation may be an early enteric signal induced by parkinsonian neurodegeneration, followed by inflammatory and dysmotility signs besides IEB modification. [Display omitted] •A short time window after induction of the PD model allowed to explore premature events in the ENS.•PD model induction produces colonic mild inflammation in mice and dryness feces.•GFAP and IBA1 increase in colonic mucosa in the 6-OHDA animal model.•Enteric glia activation in the neuromuscular layer seems to be an initial signal after PD model induction.•GDNF and Occludin protein accompany the increase in glial markers in the colonic mucosa.