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

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

Author Ghedini, Paulo César Autor UNIFESP Google Scholar
Avellar, Maria Christina Werneck Autor UNIFESP Google Scholar
Lima, Thereza Cristina Monteiro de Google Scholar
Lima-Landman, Maria Teresa Riggio de Autor UNIFESP Google Scholar
Lapa, Antonio José Autor UNIFESP Google Scholar
Souccar, Caden Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Federal de Santa Catarina (UFSC)
Amazon Biotechnol Ctr
Abstract Lack 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.
Keywords Nicotinic acetylcholine receptor
Dystrophin
Hippocampus
Memory
mdx mouse
Duchenne muscle dystrophy
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2012-11-05
Published in Brain Research. Amsterdam: Elsevier B.V., v. 1483, p. 96-104, 2012.
ISSN 0006-8993 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 96-104
Origin http://dx.doi.org/10.1016/j.brainres.2012.09.021
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000311174900011
URI http://repositorio.unifesp.br/handle/11600/35500

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