Alterations in dopaminergic activity in the large intestine of horses with pituitary pars intermedia dysfunction

Pituitary pars intermedia dysfunction (PPID) is a neurogenerative disorder in horses characterised by dopaminergic neuronal loss, resembling Parkinson’s disease. While Parkinson’s disease involves dopaminergic degeneration in both the brain and the gut, intestinal involvement in PPID has not been investigated. This study aims to investigate dopaminergic activity in the enteric nervous system (ENS) of the large intestine in horses with PPID. Archived intestinal samples from horses with PPID (pituitary grade 4/5 or 5/5 with clinical signs consistent with PPID) and aged controls (pituitary grade 1/5 or 2/5) were used. Expression of tyrosine hydroxylase (TH) and dopamine receptor-2 (D2R) were measured in the ENS of the caecum, large colon, and small colon by immunohistochemistry. Quantification of positive staining was performed on 8 ganglia per sample and averaged. Statistical comparisons were made using unpaired t-test or Mann-Whitney test for group difference, and one-way analysis of variance (ANOVA) or Kruskal-Wallis test across intestinal segments. Horses with PPID showed significantly lower TH expressions in the submucosal plexus of the caecum (control vs. PPID: 1.97% [0–16.52] vs. 0.03% [0–0.46], P = 0.042), and significantly higher D2R expression in both the submucosal plexus (0.66% [0.04–1.23] vs. 3.86% [0.06–8.93], P = 0.011) and myenteric plexus (0.28% [0.03–2.34] vs. 1.50% [0.77–5.76], P = 0.045) of the caecum. These findings provide novel evidence of altered dopaminergic signalling in the equine gut in PPID, suggesting enteric involvement in disease pathophysiology. Further research into enteric glial function and D2R targeted therapies are warranted.