Lower GDNF Serum Level Is a Possible Risk Factor for Constipation in Patients With Parkinson Disease: A Case–Control Study

Abstract

Background: Constipation is a significant symptom of Parkinson's disease (PD). Glial-derived neurotrophic factor (GDNF) is important for the morphogenesis of the enteric nervous system and plays a critical role in the preservation of mucosal integrity under enteric glia surveillance. The aim of this work was to evaluate the serum levels of GDNF in patients with PD with and without constipation.Methods: This work included 128 patients with PD. The patients were classified into three groups: those with PD but no constipation (nCons-PD) (n = 49), those with prodromal stage constipation (Cons-Pro-PD) (n = 48), and those with clinical stage constipation (Cons-Clinic-PD) (n = 31). The association between serum GDNF concentration and constipation was explored using logical regression.Results: The nCons-PD group's mean GDNF levels were 528.44 pg/ml, which was higher than the Cons-Pro-PD group's 360.72 pg/ml and the Cons-Clinic-PD group's 331.36 pg/ml. The results of binary logistic regression indicated that GDNF was a protective factor in the prevention of constipation. Cons-Clinic-PD group had a higher score of MDS-UPDRS-II, MDS-UPDRS-III, MDS-UPDRS-IV, and a higher H-Y staging as compared with nCons-PD group. Relative to the nCons-PD group, Cons-Clinic-PD had higher NMSS scores, lower MoCA and PDSS scores, and were more likely to have RBD.Conclusions: GDNF serum levels are lower in patients with PD who are constipated. A low GDNF level is a potential risk factor for constipation in patients with PD.

The Potential Application of Aloe Barbadensis Mill. as Chinese Medicine for Constipation: Mini-Review

“…A study has reported that individuals with constipation exhibit significantly lower serum levels of GDNF, potentially compromising the integrity of the intestinal mucosal barrier and hampering the efficiency of mucosal repair processes. 38 Li et al have reported that lyophilized Aloe barbadensis Mill. can effectively increase mRNA expression of GDNF, thus conferring therapeutic benefits in murine models of constipation by promoting repair processes within the intestinal intermuscular plexus, nourishing intestinal neurons, and modulating intestinal dynamics.…”

From the Gut to the Brain: The Role of Enteric Glial Cells and Their Involvement in the Pathogenesis of Parkinson’s Disease

“…The results were analyzed with binary logistic regression and suggested that GDNF may act as a protective factor in the prevention of constipation, since serum levels were lower in constipated patients with PD. The reduction in GDNF affects the integrity of the intestinal mucosal barrier, making its repair more complicated and leading to changes in intestinal permeability [88]. Inside the GI tract, enteroendocrine cells are part of the intestinal epithelium and are oriented towards the lumen.…”

Dopamine regulates colonic glial cell‐derived neurotrophic factor secretion through cholinergic dependent and independent pathways

“…PD is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Decreased GDNF levels in the serum have been observed in PD patients with constipation (Chen et al, 2021), whereas EGC protein markers are increased in the colon of patients with PD and are associated with mucosal inflammation (Clairembault et al, 2015; Devos et al, 2013; Perez‐Pardo et al, 2019). However, the relationship between dopamine (DA) and altered EGCs in the colon of patients with PD remains unknown.…”