MPTP-INDUCED PARKINSONISM REVEALS THE NATURE OF CATECHOLAMINE-CONTAINING NEURONS IN THE MOUSE ENTERIC NERVOUS SYSTEM

Parkinson’s disease (PD) is a degenerative condition which affects dopaminergic neurons of the substantia nigra, leading to movement impairment, although visceral activities, especially at gastrointestinal level, are also affected. In this study, an attempt was made to reproduce these digestive dysfunctions by using the parkinsonism-inducing neurotoxin 1-methyl, 4-phenyl, 1,2,3,6,-tetrahydropyridine (MPTP) in 9-week old C57BL mice. One week after treatment with MPTP (i.p. 20 mg/kg x3, 2 h apart) morphological and biochemical changes on the nervous network of the gut were examined: tyrosine hydroxylase (TH), dopamine (DA) transporter (DAT) and norepinephrine (NE) transporter (NET) by immunostaining; catecholamine levels by HPLC-ED. In control mice, TH immunopositivity was well evident in both myenteric and submucous plexuses, as continuous markedly stained rings. From the submucous plexus, nervous fibres and neurons extended to the mucosa up to the axes of the villi. DAT and NET immunopositivity also appeared as stained rings. In MPTP-treated mice, both TH and DAT, but not NET, immunopositive neurons decreased in both plexuses and the continuous ring-like staining was no longer evident. Consistently, while NE levels were unchanged, there was a severe DA depletion. These morphological and biochemical changes were accompanied by a functional impairment which was reminiscent of constipation occurring in PD. These data provide a reliable model to investigate the altered gastrointestinal function in PD, and offer the basis to interpret the digestive dysfunction in PD as a consequence of a selective dopaminergic loss, thus confirming that DA neurons would be the sole catecholamine cells within intrinsic circuitries affecting gut motility and secretions.