ALTERED ACETYLCHOLINE RELEASE in the HIPPOCAMPUS of DYSTROPHIN-DEFICIENT MICE

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dc.contributor.author Parames, S. F. [UNIFESP]
dc.contributor.author Coletta-Yudice, E. D. [UNIFESP]
dc.contributor.author Nogueira, F. M. [UNIFESP]
dc.contributor.author De Sousa, M. B. Nering [UNIFESP]
dc.contributor.author Hayashi, M. A. [UNIFESP]
dc.contributor.author Lima-Landman, M. T. R. [UNIFESP]
dc.contributor.author Lapa, A. J. [UNIFESP]
dc.contributor.author Souccar, C. [UNIFESP]
dc.date.accessioned 2016-01-24T14:37:27Z
dc.date.available 2016-01-24T14:37:27Z
dc.date.issued 2014-06-06
dc.identifier http://dx.doi.org/10.1016/j.neuroscience.2014.03.050
dc.identifier.citation Neuroscience. Oxford: Pergamon-Elsevier B.V., v. 269, p. 173-183, 2014.
dc.identifier.issn 0306-4522
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/37864
dc.description.abstract Mild cognitive impairments have been described in one-third of patients with Duchenne muscle dystrophy (DMD). DMD is characterized by progressive and irreversible muscle degeneration caused by mutations in the dystrophin gene and lack of the protein expression. Previously, we have reported altered concentrations of alpha 7- and beta 2-containing nicotinic acetylcholine receptors (nAChRs) in hippocampal membranes of dystrophic (mdx) mice. This suggests that alterations in the central cholinergic synapses are associated with dystrophin deficiency. in this study, we examined the release of acetylcholine (ACh) and the level of the vesicular ACh transporter (VAChT) using synaptosomes isolated from brain regions that normally have a high density of dystrophin (cortex, hippocampus and cerebellum), in control and mdx mice at 4 and 12 months of age. ACh release evoked by nicotinic stimulation or K+ depolarization was measured as the tritium outflow from superfused synaptosomes preloaded with [H-3]-choline. the results showed that the evoked tritium release was Ca2+-dependent and mostly formed by [H-3]-ACh. beta 2-containing nAChRs were involved in agonist-evoked [H-3]-ACh release in control and mdx preparations. in hippocampal synaptosomes from 12-month-old mdx mice, nAChR-evoked [H-3]-ACh release increased by 57% compared to age-matched controls. Moreover, there was a 98% increase in [H-3]-ACh release compared to 4-month-old mdx mice. [H-3]-ACh release evoked by K (+) depolarization was not altered, while the VAChT protein level was decreased (19%) compared to that of age- matched controls. in cortical and cerebellar preparations, there was no difference in nAChR-evoked [H-3]-ACh release and VAChT levels between mdx and age-matched control groups. Our previous findings and the presynaptic alterations observed in the hippocampi of 12-month-old mdx mice indicate possible dysfunction of nicotinic cholinergic synapses associated with dystrophin deficiency. These changes may contribute to the cognitive and behavioral abnormalities described in dystrophic mice and patients with DMD. (C) 2014 IBRO. Published by Elsevier B.V. All rights reserved. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 173-183
dc.language.iso eng
dc.publisher Elsevier B.V.
dc.relation.ispartof Neuroscience
dc.rights Acesso restrito
dc.subject [H-3]-ACh release en
dc.subject nicotinic acetylcholine receptor en
dc.subject vesicular ACh transporter en
dc.subject hippocampus en
dc.subject dystrophin en
dc.subject mdx mouse en
dc.title ALTERED ACETYLCHOLINE RELEASE in the HIPPOCAMPUS of DYSTROPHIN-DEFICIENT MICE en
dc.type Artigo
dc.rights.license http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Amazon Biotechnol Ctr
dc.description.affiliation Universidade Federal de São Paulo, Escola Paulista Med, Sect Nat Prod, Dept Pharmacol, BR-04044020 São Paulo, Brazil
dc.description.affiliation Amazon Biotechnol Ctr, Lab Pharmacol & Toxicol, Manaus, Amazonas, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Escola Paulista Med, Sect Nat Prod, Dept Pharmacol, BR-04044020 São Paulo, Brazil
dc.description.sponsorshipID FAPESP: 2007/02536-4
dc.description.sponsorshipID FAPESP: 2010/51344-3
dc.description.sponsorshipID FAPESP: 2008/56023-0
dc.identifier.doi 10.1016/j.neuroscience.2014.03.050
dc.description.source Web of Science
dc.identifier.wos WOS:000335903900016



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