Vulnerability of peripheral catecholaminergic neurons to MPTP is not regulated by α-synuclein
Although generally considered a prototypical movement disorder, Parkinson's disease is commonly associated with a broad-spectrum of non-motor symptoms, including autonomic dysfunctions caused by significant alterations in catecholaminergic neurons of the peripheral sympathetic nervous system. H...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-04-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996110000057 |
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| author | Marifé Cano-Jaimez Francisco Pérez-Sánchez Miguel Milán Pilar Buendía Santiago Ambrosio Isabel Fariñas |
| author_facet | Marifé Cano-Jaimez Francisco Pérez-Sánchez Miguel Milán Pilar Buendía Santiago Ambrosio Isabel Fariñas |
| author_sort | Marifé Cano-Jaimez |
| collection | DOAJ |
| description | Although generally considered a prototypical movement disorder, Parkinson's disease is commonly associated with a broad-spectrum of non-motor symptoms, including autonomic dysfunctions caused by significant alterations in catecholaminergic neurons of the peripheral sympathetic nervous system. Here we present evidence that α-synuclein is highly expressed by sympathetic ganglion neurons throughout embryonic and postnatal life and that it is found in tyrosine hydroxylase-positive sympathetic fibers innervating the heart of adult mice. However, mice deficient in α-synuclein do not exhibit any apparent alterations in sympathetic development. Sympathetic neurons isolated from mouse embryos and early postnatal mice are sensitive to the parkinsonian drug MPTP/MPP+ and intoxication requires entry of the neurotoxin through the noradrenaline transporter. Furthermore, recovery of noradrenaline from cardiac sympathetic fibers is reduced in adult mice treated with MPTP systemically. However, MPP+-induced sympathetic neuron loss in vitro or MPTP-induced cardiac noradrenaline depletion in vivo is not modified in mice lacking α-synuclein. This is in clear contrast with the observation that dopaminergic neurons of the central nervous system are significantly less vulnerable to MPTP/MPP+ in the absence of α-synuclein, suggesting different actions of this molecule in central and peripheral catecholaminergic neurons. |
| first_indexed | 2024-12-14T01:45:57Z |
| format | Article |
| id | doaj.art-e853f2f6398a43a0b6b79deae846206c |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-14T01:45:57Z |
| publishDate | 2010-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-e853f2f6398a43a0b6b79deae846206c2022-12-21T23:21:34ZengElsevierNeurobiology of Disease1095-953X2010-04-0138192103Vulnerability of peripheral catecholaminergic neurons to MPTP is not regulated by α-synucleinMarifé Cano-Jaimez0Francisco Pérez-Sánchez1Miguel Milán2Pilar Buendía3Santiago Ambrosio4Isabel Fariñas5Departamento de Biología Celular and CIBER de Enfermedades Neurodegenerativas, Universidad de Valencia, E-46100 Burjassot, SpainDepartamento de Biología Celular and CIBER de Enfermedades Neurodegenerativas, Universidad de Valencia, E-46100 Burjassot, SpainDepartamento de Biología Celular and CIBER de Enfermedades Neurodegenerativas, Universidad de Valencia, E-46100 Burjassot, SpainDepartamento de Biología Celular and CIBER de Enfermedades Neurodegenerativas, Universidad de Valencia, E-46100 Burjassot, SpainUnitat de Bioquímica, Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, E-08907 L'Hospitalet del Llobregat, SpainDepartamento de Biología Celular and CIBER de Enfermedades Neurodegenerativas, Universidad de Valencia, E-46100 Burjassot, Spain; Corresponding author. Departamento de Biología Celular, Universidad de Valencia, c/ Doctor Moliner 50, E-46100 Burjassot, Spain. Fax: +34 96354 3404.Although generally considered a prototypical movement disorder, Parkinson's disease is commonly associated with a broad-spectrum of non-motor symptoms, including autonomic dysfunctions caused by significant alterations in catecholaminergic neurons of the peripheral sympathetic nervous system. Here we present evidence that α-synuclein is highly expressed by sympathetic ganglion neurons throughout embryonic and postnatal life and that it is found in tyrosine hydroxylase-positive sympathetic fibers innervating the heart of adult mice. However, mice deficient in α-synuclein do not exhibit any apparent alterations in sympathetic development. Sympathetic neurons isolated from mouse embryos and early postnatal mice are sensitive to the parkinsonian drug MPTP/MPP+ and intoxication requires entry of the neurotoxin through the noradrenaline transporter. Furthermore, recovery of noradrenaline from cardiac sympathetic fibers is reduced in adult mice treated with MPTP systemically. However, MPP+-induced sympathetic neuron loss in vitro or MPTP-induced cardiac noradrenaline depletion in vivo is not modified in mice lacking α-synuclein. This is in clear contrast with the observation that dopaminergic neurons of the central nervous system are significantly less vulnerable to MPTP/MPP+ in the absence of α-synuclein, suggesting different actions of this molecule in central and peripheral catecholaminergic neurons.http://www.sciencedirect.com/science/article/pii/S0969996110000057α-Synuclein knockoutNeurotrophic factorPeripheral nervous systemSympathetic nervous systemAutonomic gangliaMPP+ |
| spellingShingle | Marifé Cano-Jaimez Francisco Pérez-Sánchez Miguel Milán Pilar Buendía Santiago Ambrosio Isabel Fariñas Vulnerability of peripheral catecholaminergic neurons to MPTP is not regulated by α-synuclein Neurobiology of Disease α-Synuclein knockout Neurotrophic factor Peripheral nervous system Sympathetic nervous system Autonomic ganglia MPP+ |
| title | Vulnerability of peripheral catecholaminergic neurons to MPTP is not regulated by α-synuclein |
| title_full | Vulnerability of peripheral catecholaminergic neurons to MPTP is not regulated by α-synuclein |
| title_fullStr | Vulnerability of peripheral catecholaminergic neurons to MPTP is not regulated by α-synuclein |
| title_full_unstemmed | Vulnerability of peripheral catecholaminergic neurons to MPTP is not regulated by α-synuclein |
| title_short | Vulnerability of peripheral catecholaminergic neurons to MPTP is not regulated by α-synuclein |
| title_sort | vulnerability of peripheral catecholaminergic neurons to mptp is not regulated by α synuclein |
| topic | α-Synuclein knockout Neurotrophic factor Peripheral nervous system Sympathetic nervous system Autonomic ganglia MPP+ |
| url | http://www.sciencedirect.com/science/article/pii/S0969996110000057 |
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