Quantitative changes of nicotinic receptors in the hippocampus of dystrophin-deficient mice

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dc.contributor.authorGhedini, Paulo César [UNIFESP]
dc.contributor.authorAvellar, Maria Christina Werneck [UNIFESP]
dc.contributor.authorLima, Thereza Cristina Monteiro de
dc.contributor.authorLima-Landman, Maria Teresa Riggio de [UNIFESP]
dc.contributor.authorLapa, Antonio José [UNIFESP]
dc.contributor.authorSouccar, Caden [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Federal de Santa Catarina (UFSC)
dc.contributor.institutionAmazon Biotechnol Ctr
dc.date.accessioned2016-01-24T14:28:00Z
dc.date.available2016-01-24T14:28:00Z
dc.date.issued2012-11-05
dc.description.abstractLack of dystrophin in Duchenne muscle dystrophy (DMD) and in the mutant mdx mouse results in progressive muscle degeneration, structural changes at the neuromuscular junction, and destabilization of the nicotinic acetylcholine receptors (nAChRs). One-third of DMD patients also present non-progressive cognitive impairments. Considering the role of the cholinergic system in cognitive functions, the number of nAChR binding sites and the mRNA levels of alpha 4, beta 2, and alpha 7 subunits were determined in brain regions normally enriched in dystrophin (cortex, hippocampus and cerebellum) of mdx mice using specific ligands and reverse-transcription polymerase chain reaction assays, respectively. Membrane preparations of these brain regions were obtained from male control and mdx mice at 4 and 12 months of age. the number of [H-3]-cytisine (alpha 4 beta 2) and [I-125]-alpha-bungarotoxin ([I-125]-alpha BGT, alpha 7) binding sites in the cortex and cerebellum was not altered with age or among age-matched control and mdx mice. A significant reduction in [H-3]-cytisine (48%) and [I-125]-alpha BGT (37%) binding sites was detected in the hippocampus of mdx mice at 12 months of age. When compared with the age-matched control groups, the mdx mice did not have significantly altered [H-3]-cytisine binding in the hippocampus, but [I-125]-alpha BGT binding in the same brain region was 52% higher at 4 months and 20% lower at 12 months. mRNA transcripts for the nAChR alpha 4, beta 2, and alpha 7 subunits were not significantly altered in the same brain regions of all animal groups. These results suggest a potential alteration of the nicotinic cholinergic function in the hippocampus of dystrophin-deficient mice, which might contribute to the impairments in cognitive functions, such as learning and memory, that have been reported in the dystrophic murine model and DMD patients. (C) 2012 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Sect Nat Prod, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Sect Expt Endocrinol, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliationUniv Fed Santa Catarina, Dept Pharmacol, Neuropharmacol Lab, Florianopolis, SC, Brazil
dc.description.affiliationAmazon Biotechnol Ctr, Lab Pharmacol & Toxicol, Manaus, AM, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Sect Nat Prod, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Sect Expt Endocrinol, Dept Pharmacol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent96-104
dc.identifierhttp://dx.doi.org/10.1016/j.brainres.2012.09.021
dc.identifier.citationBrain Research. Amsterdam: Elsevier B.V., v. 1483, p. 96-104, 2012.
dc.identifier.doi10.1016/j.brainres.2012.09.021
dc.identifier.fileWOS000311174900011.pdf
dc.identifier.issn0006-8993
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/35500
dc.identifier.wosWOS:000311174900011
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofBrain Research
dc.rightsAcesso aberto
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectNicotinic acetylcholine receptoren
dc.subjectDystrophinen
dc.subjectHippocampusen
dc.subjectMemoryen
dc.subjectmdx mouseen
dc.subjectDuchenne muscle dystrophyen
dc.titleQuantitative changes of nicotinic receptors in the hippocampus of dystrophin-deficient miceen
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