vasoactive-intestinal-peptide and Parkinson-Disease--Secondary

In the present study, the effect of systemically administered vasoactive intestinal peptide (VIP) (25 ng/kg i.p.) was investigated on drug-induced rotational behavior, extra-cellular dopamine levels and histology of corpus striatum in a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease. After 15 days of 6-OHDA lesion, apomorphine-induced (0.05 mg/kg s.c.) rotational behavior of the animals significantly increased and extra-cellular dopamine levels of corpus striatum were significantly reduced. VIP reversed the rotational deficits but did not alter the decrease in striatal dopamine levels. On the other hand, histological data indicate that VIP significantly reduced neuronal death and demyelination. Electron microscopic appearance of mast cells showed ultra-structural variety between VIP-treated and 6-OHDA lesioned groups. VIP activates mast cells without any evidence of typical exocytosis, and possibly mast cells could participate in neuroprotection. Our results suggest that systemically administered VIP can attenuate the motor response changes, neuronal cell death, and myelin sheet loss characteristically associated with 12 microg 6-OHDA administration into the rat striatum. Brain mast cells seem to participate in neuronal protection. Possibly, protective cues could be produced by brain mast cells.

Topics: Animals; Behavior, Animal; Brain; Disease Models, Animal; Dopamine; Mast Cells; Microdialysis; Neuroprotective Agents; Parkinson Disease, Secondary; Rats; Vasoactive Intestinal Peptide

Neurochemical studies of post-mortem human parkinsonian brains have demonstrated specific alterations in neuropeptide concentrations within the substantia nigra and striatal structures. The drug, 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP) has been reported to act as a selective toxin to nigrostriatal dopamine neurons, and induces a parkinsonian-like syndrome in primates. In this study, marmosets developed features typical of Parkinson's disease following treatment with MPTP for four days. The effects of MPTP treatment on the concentrations of dopamine and neuropeptides were determined and changes compared with those reported for Parkinson's disease. It was found that within the substantia nigra, substance P concentrations doubled following treatment with MPTP; in contrast, concentrations of vasoactive intestinal peptide and neuropeptide Y were significantly reduced. No changes were observed in the concentrations of six other neuropeptides measured in this region, notably cholecystokinin. Despite marked depletion of dopamine within the caudate nucleus and putamen, concentrations of all neuropeptides within these structures remained unchanged with the exception of an isolated reduction of neuropeptide Y within the putamen. Somatostatin concentrations within the frontal cortex and hippocampus were significantly elevated in the marmosets treated with MPTP. These neuropeptide changes in the CNS contrast with those reported for Parkinson's disease. In view of the autonomic dysfunction associated with Parkinson's disease, peripheral concentrations of neuropeptides were determined. Significant depletion of neuropeptide Y was identified in the ureter, adrenal and cardiovascular tissue. Thus the neurochemical changes induced by MPTP may not be as selective as previously reported.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Brain Chemistry; Callitrichinae; Cholecystokinin; Disease Models, Animal; Dopamine; Female; Kidney; Male; Neurotensin; Parkinson Disease, Secondary; Pyridines; Substance P; Vasoactive Intestinal Peptide