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Loss of spinal motor neurons and alteration of alpha-synuclein immunostaining in MPTP induced Parkinsonism in mice.
J Chem Neuroanat. 2012 Jul; 44(2):76-85.JC

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+Show Affiliations

Department of Anatomic, Histologic, Forensic and Locomotor Apparatus Sciences, Sapienza University of Rome, Via A. Borelli 50, 00161 Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22580273

Citation

Vivacqua, Giorgio, et al. "Loss of Spinal Motor Neurons and Alteration of Alpha-synuclein Immunostaining in MPTP Induced Parkinsonism in Mice." Journal of Chemical Neuroanatomy, vol. 44, no. 2, 2012, pp. 76-85.
Vivacqua G, Biagioni F, Yu S, et al. Loss of spinal motor neurons and alteration of alpha-synuclein immunostaining in MPTP induced Parkinsonism in mice. J Chem Neuroanat. 2012;44(2):76-85.
Vivacqua, G., Biagioni, F., Yu, S., Casini, A., Bucci, D., D'Este, L., & Fornai, F. (2012). Loss of spinal motor neurons and alteration of alpha-synuclein immunostaining in MPTP induced Parkinsonism in mice. Journal of Chemical Neuroanatomy, 44(2), 76-85. https://doi.org/10.1016/j.jchemneu.2012.04.003
Vivacqua G, et al. Loss of Spinal Motor Neurons and Alteration of Alpha-synuclein Immunostaining in MPTP Induced Parkinsonism in Mice. J Chem Neuroanat. 2012;44(2):76-85. PubMed PMID: 22580273.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of spinal motor neurons and alteration of alpha-synuclein immunostaining in MPTP induced Parkinsonism in mice. AU - Vivacqua,Giorgio, AU - Biagioni,Francesca, AU - Yu,Shun, AU - Casini,Arianna, AU - Bucci,Domenico, AU - D'Este,Loredana, AU - Fornai,Francesco, Y1 - 2012/05/08/ PY - 2012/01/21/received PY - 2012/04/29/revised PY - 2012/04/30/accepted PY - 2012/5/15/entrez PY - 2012/5/15/pubmed PY - 2013/1/5/medline SP - 76 EP - 85 JF - Journal of chemical neuroanatomy JO - J Chem Neuroanat VL - 44 IS - 2 N2 - 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. SN - 1873-6300 UR - https://www.unboundmedicine.com/medline/citation/22580273/Loss_of_spinal_motor_neurons_and_alteration_of_alpha_synuclein_immunostaining_in_MPTP_induced_Parkinsonism_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-0618(12)00021-X DB - PRIME DP - Unbound Medicine ER -