title: Loss of spinal motor neurons and alteration of alpha-synuclein immunostaining in MPTP induced Parkinsonism in mice.
abstract: 1-Methyl, 4-phenyl, 1,2,3,6-tetrahydropiridine (MPTP) is a neurotoxin, widely used to produce experimental models of Parkinson Disease in rodents and primates. Although dopaminergic neurons are the most sensitive to MPTP neurotoxicity, different neuronal subtypes are affected. Among these, recent studies indicate that MPTP may produce pathological effects on spinal neurons. In fact, MPTP activates apoptotic proteins within the spinal cord and in particular within the motor neurons, suggesting commonalities between Parkinson Disease and Amyotrophic Lateral Sclerosis. In order to assess this point, in the present study we measured whether MPTP produces motor neurons loss. We chose a dose of MPTP (20 mg/kg × 3, 2 h apart), which in C57BL/6N mice was able to induce a massive nigrostriatal damage. Since both Parkinson Disease and Amyotrophic Lateral Sclerosis are characterized by altered alpha-synuclein immunostaining, this protein was also evaluated within spinal motor neurons, following MPTP administration. Three different monoclonal antibodies, recognizing distinct epitopes in the sequence of alpha-synuclein were used. Severe dopaminergic cell loss was quantified by stereology within the substantia nigra pars compacta, along with marked decrease of striatal tyrosine hydroxylase densitometry. The same doses of MPTP also caused a significant motor neuron loss in the spinal cord (roughly 30%). Spared motor neurons appeared often dysmorphic and vacuolated and possessed altered alpha-synuclein immunostaining. This latter finding extended to other cell types of the spinal cord. These data indicate that MPTP, apart from being a dopaminergic neurotoxin, produces also motor neuron death, thus bridging experimental Parkinsonism and motor neuron disease.
authors.affiliation: Department of Anatomic, Histologic, Forensic and Locomotor Apparatus Sciences, Sapienza University of Rome, Via A. Borelli 50, 00161 Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Vivacqua
authors.forename: Francesca
authors.initials: F
authors.lastname: Biagioni
authors.forename: Shun
authors.initials: S
authors.lastname: Yu
authors.forename: Arianna
authors.initials: A
authors.lastname: Casini
authors.forename: Domenico
authors.initials: D
authors.lastname: Bucci
authors.forename: Loredana
authors.initials: L
authors.lastname: D'Este
authors.forename: Francesco
authors.initials: F
authors.lastname: Fornai
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count / Q000379:methods; D003342:Corpus Striatum / Q000276:immunology / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000276:immunology / Q000378:metabolism; D051844:alpha-Synuclein / Q000276:immunology / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase