title: Evaluation of nigrostriatal neurodegeneration and neuroinflammation following repeated intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in mice, an experimental model of Parkinson's disease.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population older than 60 years. The administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice is the most widely used approach to elucidate the mechanisms of cell death involved in PD. However, the magnitude of the PD-like neurodegeneration induced by MPTP depends on many variables, including the regimen of its administration. It has been demonstrated that intranasal (i.n.) administration of MPTP constitutes a new route of toxin delivery to the brain that mimics environmental exposure to neurotoxins. Previous data showed that mice submitted to chronic and acute i.n. MPTP treatment displayed a robust (~80%) and moderate (~55%) loss of striatal dopamine, respectively. However, little is known about the neurodegenerative and neuroinflammatory processes following a subacute i.n. MPTP administration in mice. Here, the C57BL/6 mice were infused intranasally with MPTP (1 mg/nostril/day) during 4 consecutive days. At 7 and 28 days after the last administration, the subacute i.n. MPTP regime decreased the tyrosine hydroxylase (TH)-labeling in the striatum (40-50%) and substantia nigra (25-30%) and increased the astrogliosis in such brain areas at both time points. Taken together, our data showed that the subacute administration of MPTP into the nasal cavity of C57BL/6 mice induces long-lasting neurodegeneration and neuroinflammation in the nigrostriatal pathway, thus representing a valuable animal model for the investigation of neuroprotective strategies in PD.
authors.affiliation: INSERM, UMR 975, CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Paris, France.
authors.forename: Fabrine S M
authors.initials: FS
authors.lastname: Tristão
authors.forename: Majid
authors.initials: M
authors.lastname: Amar
authors.forename: Ines
authors.initials: I
authors.lastname: Latrous
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Del-Bel
authors.forename: Rui D
authors.initials: RD
authors.lastname: Prediger
authors.forename: Rita
authors.initials: R
authors.lastname: Raisman-Vozari
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D004781:Environmental Exposure; D007249:Inflammation / Q000473:pathology; D020267:MPTP Poisoning / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000473:pathology; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology*
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine