Parkinson's Disease (PD), the second most common neurodegenerative disorder worldwide (Sharma et al., 2024), is characterized by motor dysfunctions such as tremor, rigidity, bradykinesia, and postural instability. In addition to typical motor impairments (Seppi et al., 2019), the non-motor features including symptoms such as sleep disorders, pain, and autonomic dysfunction (Chaudhuri et al., 2005). Among autonomic dysfunctions, gastrointestinal disturbances commonly manifest as bloating (abdominal distension), constipation (difficulty passing stool), and defecatory dysfunction (difficulty with bowel movements) (Fasano et al., 2015). PD patients also frequently experience significantly delayed colonic transit time and increased colonic volume (Knudsen et al., 2017), with 80–90 % of cases reporting constipation (Edwards et al., 1993), which severely impacts quality of life.

To investigate the mechanisms underlying the non-motor symptoms such as constipation due to gastrointestinal dysfunction in PD, extensive research has been conducted. Some studies propose that constipation in PD patients results from impaired central nervous system regulation of gastrointestinal motility and hormone secretion, which is closely linked to dopaminergic neuron dysfunction (Al-Kuraishy et al., 2024a; Travagli et al., 2020). Reduced dopamine levels cause gastrointestinal motility disorders and delayed intestinal reflexes, contributing to constipation (Barboza et al., 2015). Alterations in gastrointestinal permeability have been associated with changes in tight junction-related molecules, including claudin, ZO-1, and occludin (Hu et al., 2020; Chelakkot et al., 2018; Sun et al., 2020). Research has shown significantly reduced occludin expression in colon specimens of PD patients, with altered cellular distribution of claudin and ZO-1 in colon mucosal specimens (Clairembault et al., 2015).

The gastrointestinal dyskinesia in an MPTP-induced PD mouse model reported loss of intestinal dopaminergic neurons, increased α-synuclein accumulation and associated changes in colonic motility, although it did not assess intestinal barrier disruption (Anderson et al., 2007; Lai et al., 2018). In 6-OHDA-induced PD rhesus monkeys, significant reductions in colonic TH expression were observed, but no significant changes were detected in panneuronal markers (PGP9.5) or PD-related phosphorylated α-synuclein (Shultz et al., 2016).

On the one hand, the detailed pathological studies of intestinal structure and function in PD patients remain limited, which may be due to rareness of the intestinal biopsy or autopsy tissues from PD patients, others, no similar studies have been reported in animal experiments. Therefore, there is still a lack of comprehensive understanding of the histopathological changes of intestinal structure and function in clinical PD patients, which also limits the further exploration of the underlying mechanism of non-motor symptoms such as constipation in PD patients.

In this study, a typical PD monkey model exhibiting typical symptoms, sustained stability, and pathological evidence of significant dopamine neuron reduction in the SN was employed. Four intestinal segments including duodenum, ileum, transverse colon, and rectum were collected, and the intestinal mucosal structure, intestinal barrier integrity, peristalsis (c-kit), and innervation (PGP9.5/TH expression) were systematically evaluated. This study aims to perform a comprehensive evaluation of intestinal structure and function in PD monkeys, and so as to explore the effects of central dopamine regulation disorders on mediating the intestinal dysfunction in PD monkeys, and potentially provide a scientific basis for understanding PD-related intestinal symptoms and developing potential intervention strategies.