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http://hdl.handle.net/10261/147499
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dc.contributor.author | Pavia-Collado, Rubén | - |
dc.contributor.author | Ruiz-Bronchal, Esther | - |
dc.contributor.author | Campa, Leticia | - |
dc.contributor.author | Artigas, Francesc | - |
dc.contributor.author | Bortolozzi, Analía | - |
dc.date.accessioned | 2017-03-29T07:04:19Z | - |
dc.date.available | 2017-03-29T07:04:19Z | - |
dc.date.issued | 2016-10-06 | - |
dc.identifier.citation | X Simposi de Neurobiologia (2016) | - |
dc.identifier.uri | http://hdl.handle.net/10261/147499 | - |
dc.description | Trabajo presentado en el X Simposi de Neurobiologia, celebrado en Barcelona, España, el 6 y 7 de octubre de 2016 | - |
dc.description.abstract | Synucleins are small, highly conserved proteins in vertebrates, especially abundant in neurons and typically enriched in presynaptic terminals. Mutations in ¿-synuclein gene have been reported in families susceptible to inherited forms of Parkinson¿s disease, but far less is known about other members of the synuclein family (ß- and ¿-synucleins), which have been implicated in the pathophysiology of neurodegenerative diseases and several synucleinopathies. Here, we examined the distribution and cellular localization of ¿-synuclein in the mouse brain using in situ hybridization and immunohistochemistry procedures, and we evaluated the functional role of ¿-synuclein in nigrostriatal dopamine (DA) neurotransmission in vivo. We used two different models with: 1) down-regulated ¿-synuclein expression specifically in DA neurons of substantia nigra compacta/ventral tegmental area (SNc/VTA) by small interfering RNA molecules (siRNA), or 2) over-expressed ¿-synuclein in SNc/VTA DA neurons using AAV10-CMV-mouse-¿-synuclein vector. In C57BL/6J control mice, abundant levels of ¿-synuclein mRNA were found in the monoaminergic nuclei including SNc, VTA, raphe nuclei and locus coeruleus, as well as in the habenular nuclei. Double in situ hybridization and immunohistochemistry showed a specific colocalization of ¿-synuclein in TH-positive DA neurons. Unilateral infusion of three siRNA sequences targeting ¿-synuclein (4.2 nmol) decreased ¿-synuclein mRNA levels in DA neurons of SNpc (50% and 80% of aCSF-treated mice 24h and 72h post-infusion, respectively). Furthermore, ¿-synuclein suppression displayed an enhanced striatal DA tone using intracerebral microdialysis, which is reflected in higher extracellular DA levels in siRNA-treated mice during local veratridine (50 ¿M), nomifensine (1-10-50 ¿M) and amphetamine (1-10-100 ¿M) administrations and lower levels with quinpirole (10 ¿M). Meanwhile, ¿-synuclein over-expression led to lower extracellular DA levels during nomifensine (1-10-50 ¿M) administration. In conclusion, these results confirm that ¿- synuclein is a negative regulator of DA neurotransmission and suggest that siRNA-induced ¿-synuclein suppression in midbrain dopaminergic neurons may lead to new therapies for synucleinopathies. | - |
dc.rights | closedAccess | - |
dc.title | Regulation of nigrostriatal dopamine neurotransmission by gamma-synuclein: down- and over-expression mouse models | - |
dc.type | comunicación de congreso | - |
dc.date.updated | 2017-03-29T07:04:19Z | - |
dc.description.version | Peer Reviewed | - |
dc.language.rfc3066 | eng | - |
dc.relation.csic | Sí | - |
dc.type.coar | http://purl.org/coar/resource_type/c_5794 | es_ES |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
item.fulltext | No Fulltext | - |
item.openairetype | comunicación de congreso | - |
Aparece en las colecciones: | (IIBB) Comunicaciones congresos |
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