The degeneration of nigral dopaminergic neurons in Parkinson's disease is believed to be associated with a glial reaction and inflammatory changes. In turn, local factors may induce changes in vascularization and contribute to neuronal vulnerability. Among these factors, Vascular Endothelial Growth Factor (VEGF) is released in adults under pathological conditions and is thought to induce angiogenesis. In order to determine whether changes in brain vasculature are observed in the affected brain regions in parkinsonism, we quantitatively analysed the VEGF-expressing cells and blood vessels in the substantia nigra of monkeys rendered parkinsonian by MPTP injection and compared the results with those obtained in control monkeys. Using stereological methods, we observed an increase in the number of VEGF-expressing neurons and an increase of the number of blood vessels and their volume occupying the substantia nigra pars compacta of monkeys rendered parkinsonian by chronic MPTP intoxication. These changes in vascularization may therefore modify the neuronal availability of blood nutrients, blood cells or toxic substances and neuronal susceptibility to parkinsonism.
The aim of this study was to investigate whether prolactin, melatonin and cortisol are altered in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and if so, whether MPTP may alter the availability of these hormones in chronic experimental parkinsonism. Furthermore, vegetative and sleep disorders have been described in both parkinsonian patients and in MPTP chronic monkeys; these may result indirectly from concomitant hormonal variations. Seven adult male cynomolgus monkeys were used for this experiment. Five were treated with systemic doses of intravenous MPTP but not with L-DOPA or dopaminergic agonists. In their 3rd year of parkinsonism, plasma samples were obtained day and night at 3-hour intervals. Sample collection was repeated three times for each animal. Prolactin, melatonin and cortisol concentrations were determined by enzyme immunoassay and compared with samples taken from the control group. Both MPTP-treated monkeys and the control group displayed a similar secretion pattern for the three hormones, except at several specific times when prolactin and melatonin showed significant differences. No changes were found for cortisol. The results suggest a possible alteration of hormonal metabolism in chronic MPTP parkinsonian monkeys.
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