Chronic alterations in jejunal myoelectric activity in rats due to MPTP

Abstract

Parkinsonian patients may have symptoms consistent with intestinal pseudo-obstruction, but a primary intestinal abnormality has not been shown. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), after conversion to a toxic metabolite via the monoamine oxidase system, can induce Parkinson's disease by destroying dopaminergic neurons in the substantia nigra in humans and primates. Rodents have some catecholamine depletion but much less so than primates. Using chronic bipolar electrodes on the proximal jejunum of Wistar rats, we show significant, chronic migrating myoelectric complex disruption (P less than 0.001) and prolongation of irregular spike activity (P less than 0.001). Pargyline (a monoamine oxidase inhibitor) pretreatment significantly blocked these myoelectric changes. Sinemet (L-dopa and carbidopa), given after MPTP to replete dopamine, decreased the MPTP-induced migrating myoelectric complex disruption. Jejunal myenteric plexus dopamine levels were significantly decreased (to 61% of control) after MPTP but after much higher doses than were required to disrupt migrating myoelectric complex activity (180 mg/kg total vs. 30 mg/kg). Dopamine in the central nervous system was not depleted. We conclude that MPTP causes intestinal myoelectric disruption (which can be blocked by pargyline and decreased by Sinemet) possibly through enteric, but not central, nervous system effects.

Circadian Dysfunction in a Rotenone-Induced Parkinsonian Rodent Model

“…This result agrees with several previous reports in which a decrease in body temperature was observed in PD patients (Cagnacci et al, 1990), 6-OHDA-lesioned rats (Boulamery et al, 2010), and MPTP-treated rats (Eaker et al, 1987), mice (Freyaldenhoven et al, 1995;Miller & O'Callaghan, 1994), and monkeys (Almirall et al, 2001). The BT reduction could be attributed, at least in part, to the lower level of motor activity induced by rotenone.…”

Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic Parkinsonism

“…The deviation in frequency of defaecation from that of healthy age/gender‐matched controls [25,26], precedes diagnosis by, on average, three decades. Indeed, depletion of jejunal dopamine, with levodopa‐responsive hypomotility, is a forerunner of parkinsonism in the MPTP (1‐methyl‐4‐phenyl‐1,2,3,6 tetrahydropyridine) animal‐model [27]. Degeneration of vagal motor‐nuclei is well‐described in idiopathic parkinsonism, but the colon also shows degenerative changes.…”

Parkinson’s disease and the gut: a well known clinical association in need of an effective cure and explanation

“…Dopamine seems to be a major candidate for the impairment of GI function in PD since its levels were found to be decreased in the ascending colon from PD patients (Table 1). 6 Although the gut contains DA, 5 only recently this catecholamine has been confirmed as an intrinsic neurotransmitter of the ENS. In fact, DA, tyrosine hydroxylase (TH), and the DA transporter (DAT) co‐localize within a subset of ENS neurons 35 .…”

“…In fact, while the alterations of the motor systems in PD are extensively investigated, the influence of the disease at peripheral level with an emphasis on autonomic musculature and glands in the digestive system still needs to be clarified and has not been explored in detail. Only a few suitable experimental models have been proposed to investigate GI dysfunction 4,5 . Thus, there is a strong discrepancy between the high prevalence and variety of GI symptoms occurring in PD and the lack of research in this area.…”