Restoring Colon Motility in Parkinson's Disease: Gdnf-Mediated Cx43 Suppression in Reactive Enteric Glial Cells

Abstract Background:Constipation is most common in patients with Parkinson's disease (PD) and is usually caused by slow colon movement. Intestinal glial cells (EGCs) play a role in the regulation of intestinal inflammation and movement, and their activation can trigger the death of intestinal neurons, which may be mediated by the activation of the connexin 43 (CX43) semi-channel. GDNF plays an important role in maintaining intestinal movement and inhibiting inflammation. This study investigated whether GDNF plays an inhibitory role in the activation of EGCs by inflammation, and promotes neuronal survival and regulates intestinal motility through the EGCS-CX43 pathway. Methods: PD model was established by unilateral stereotaxic injection of 6-hydroxydopamine. At the 5th week after injury, AAV5-GDNF (2~5×1011) was intraperitoneally injected into experimental and control rats. Fecal moisture percentage (FMP) and toner propulsion rate (CPPR) were used to evaluate colon motion. Colon-related markers were detected at 5 and 10 weeks after induction. Results:Colonic motility and GDNF expression decreased, EGCs reactivity, IL-1, IL-6, TNF-α expression increased, CX43 up-regulated, PGP 9.5 decreased. Intraperitoneal injection of AAV-GDNF can protect colon neurons by inhibiting EGCs activation and down-regulating CX43. Conclusion: GDNF may promote the survival of colonic neurons in PD rats by regulating CX43 activity.