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Motor Neurons Pathology After Chronic Exposure to MPTP in Mice

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Abstract

The neurotoxin 1-methyl,4-phenyl-1,2,3,6-tetrahydropiridine (MPTP) is widely used to produce experimental parkinsonism in rodents and primates. Among different administration protocols, continuous or chronic exposure to small amounts of MPTP is reported to better mimic cell pathology reminiscent of Parkinson’s disease (PD). Catecholamine neurons are the most sensitive to MPTP neurotoxicity; however, recent studies have found that MPTP alters the fine anatomy of the spinal cord including motor neurons, thus overlapping again with the spinal cord involvement documented in PD. In the present study, we demonstrate that chronic exposure to low amounts of MPTP (10 mg/kg daily, × 21 days) significantly reduces motor neurons in the ventral lumbar spinal cord while increasing α-synuclein immune-staining within the ventral horn. Spinal cord involvement in MPTP-treated mice extends to Calbindin D28 KDa immune-reactive neurons other than motor neurons within lamina VII. These results were obtained in the absence of significant reduction of dopaminergic cell bodies in the Substantia Nigra pars compacta, while a slight decrease was documented in striatal tyrosine hydroxylase immune-staining. Thus, the present study highlights neuropathological similarities between dopaminergic neurons and spinal motor neurons and supports the pathological involvement of spinal cord in PD and experimental MPTP-induced parkinsonism. Remarkably, the toxic threshold for motor neurons appears to be lower compared with nigral dopaminergic neurons following a chronic pattern of MPTP intoxication. This sharply contrasts with previous studies showing that MPTP intoxication produces comparable neuronal loss within spinal cord and Substantia Nigra.

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Funding

This study was funded by University La Sapienza Roma, Ateneo 2012–2015, and Ministero della Salute, Ricerca Corrente 2019.

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Authors and Affiliations

  1. Department of Anatomy, Histology, Forensic Medicine and Locomotor Sciences, Via A. Borelli 50, 00161, Rome, Italy

    Giorgio Vivacqua & Loredana D’Este

  2. Department of Neurobiology, Xuan Wu Hospital, Capital University of Medical Sciences, 45 Changchun St, Beijing, 100053, China

    Giorgio Vivacqua & Shun Yu

  3. I.R.C.C.S. Neuromed, Via Atinense, 18, Pozzilli, Italy

    Francesca Biagioni, Carla L. Busceti, Michele Madonna & Francesco Fornai

  4. Department of Traslational Research and New Technologies in Medicine and Surgery, University of Pisa, via Roma 55, 56126, Pisa, Italy

    Michela Ferrucci, Larisa Ryskalin & Francesco Fornai

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  1. Giorgio Vivacqua
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  2. Francesca Biagioni
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  3. Carla L. Busceti
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  4. Michela Ferrucci
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  5. Michele Madonna
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  6. Larisa Ryskalin
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  7. Shun Yu
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  8. Loredana D’Este
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  9. Francesco Fornai
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Contributions

Original draft preparation [Giorgio Vivacqua, Francesco Fornai]; animal treatments [Giorgio Vivacqua, Francesca Biagioni]; immune-histochemistry [Giorgio Vivacqua, Francesca Biagioni]; SDS Page Immune-blotting [Francesca Biagioni]; stereology [Carla L. Busceti]; anti-alpha-synuclein 2E3 and 3D5 primary antibodies set-up [Shun Yu]; data analysis [Giorgio Vivacqua, Francesca Biagioni, Carla L. Busceti, Michela Ferrucci]; animal care [Michele Madonna]; writing the paper and editing [Michela Ferrucci, Larisa Ryskalin, Loredana D’Este, Francesco Fornai]; conceptualization, intellectual content, and supervision [Francesco Fornai].

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Correspondence to Francesco Fornai.

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Vivacqua, G., Biagioni, F., Busceti, C.L. et al. Motor Neurons Pathology After Chronic Exposure to MPTP in Mice. Neurotox Res 37, 298–313 (2020). https://doi.org/10.1007/s12640-019-00121-y

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