Neuroprotective effect of vasoactive intestinal peptide (VIP) in a mouse model of Parkinson's disease by blocking microglial activation.
Parkinson's disease (PD) is a common neurodegenerative disorder with no effective protective treatment, characterized by a massive degeneration of dopaminergic neurons in the substantia nigra (SNpc) and the subsequent loss of their projecting nerve fibers in the striatum. To elucidate PD pathogenic factors, and thus to develop therapeutic strategies, a murine PD model based on the administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been used extensively. It has been demonstrated that activated microglia cells actively participate in the pathogenesis of MPTP-induced PD through the release of cytotoxic factors. Because current treatments for PD are not effective, considerable research focused lately on a number of regulatory molecules termed microglia-deactivating factors. Vasoactive intestinal peptide (VIP), a neuropeptide with a potent anti-inflammatory effect, has been found to be protective in several inflammatory disorders. This study investigates the putative protective effect of VIP in the MPTP model for PD. VIP treatment significantly decreases MPTP-induced dopaminergic neuronal loss in SNpc and nigrostriatal nerve-fiber loss. VIP prevents MPTP-induced activation of microglia in SNpc and striatum and the expression of the cytotoxic mediators, iNOS, interleukin 1beta, and numor necrosis factor alpha. VIP emerges as a potential valuable neuroprotective agent for the treatment of pathologic conditions in the central nervous system, such as PD, where inflammation-induced neurodegeneration occurs.
Delgado
Mario
M
Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA. mariodm@bio.ucm.es
Ganea
Doina
D
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D007375:Interleukin-1 / Q000235:genetics; D020267:MPTP Poisoning / Q000378:metabolism / Q000517:prevention & control*; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D015259:Dopamine Agents; D007375:Interleukin-1; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014660:Vasoactive Intestinal Peptide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine