Altered striatal endocannabinoid signaling in a transgenic mouse model of spinocerebellar ataxia type-3

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dc.contributor.authorHernández-Gálvez, Mariluz
dc.contributor.authorHillard, Cecilia J.
dc.contributor.authorMaciel, Patricia
dc.contributor.authorValdeolivas, Sara
dc.contributor.authorRodríguez Cueto, Carmen Aurora
dc.contributor.authorGómez Ruiz, María Sagrario
dc.contributor.authorFernández Ruiz, José Javier
dc.contributor.authorRamos Atance, José Antonio
dc.contributor.editorDavid R Borchelt
dc.date.accessioned2024-01-15T18:32:39Z
dc.date.available2024-01-15T18:32:39Z
dc.date.issued2017-04-27
dc.description.abstractSpinocerebellar ataxia type-3 (SCA-3) is the most prevalent autosomal dominant inherited ataxia. We recently found that the endocannabinoid system is altered in the post-mortem cerebellum of SCA-3 patients, and similar results were also found in the cerebellar and brainstem nuclei of a SCA-3 transgenic mouse model. Given that the neuropathology of SCA-3 is not restricted to these two brain regions but rather, it is also evident in other structures (e.g., the basal ganglia), we studied the possible changes to endocannabinoid signaling in the striatum of these transgenic mice. SCA-3 mutant mice suffer defects in motor coordination, balance and they have an abnormal gait, reflecting a cerebellar/brainstem neuropathology. However, they also show dystonia-like behavior (limb clasping) that may be related to the malfunction/deterioration of specific neurons in the striatum. Indeed, we found a loss of striatal projecting neurons in SCA-3 mutant mice, accompanied by a reduction in glial glutamate transporters that could potentially aggravate excitotoxic damage. In terms of endocannabinoid signaling, no changes in CB2 receptors were evident, yet an important reduction in CB1 receptors was detected by qPCR and immunostaining. The reduction in CB1 receptors was presumed to occur in striatal afferent and efferent neurons, also potentially aggravating excitotoxicity. We also measured the endocannabinoid lipids in the striatum and despite a marked increase in the FAAH enzyme in this area, no overall changes in these lipids were found. Collectively, these studies confirm that the striatal endocannabinoid system is altered in SCA-3 mutant mice, adding to the equivalent changes found in other strongly affected CNS structures in this type of ataxia (i.e.: the cerebellum and brainstem). These data open the way to search for drugs that might correct these changes.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.doi10.1371/journal.pone.0176521
dc.identifier.issn1932-6203
dc.identifier.officialurlhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176521
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93218
dc.journal.titlePLOS one
dc.language.isoeng
dc.publisherPLOS
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu61
dc.subject.ucmCiencias Biomédicas
dc.subject.unesco24 Ciencias de la Vida
dc.titleAltered striatal endocannabinoid signaling in a transgenic mouse model of spinocerebellar ataxia type-3
dc.typejournal article
dc.type.hasVersionVoR
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscoverya19d29d6-cf5c-4a37-881e-606e18e3efca
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