ALTERED ACETYLCHOLINE RELEASE IN THE HIPPOCAMPUS OF DYSTROPHIN-DEFICIENT MICE

Autor(es)

Parames, S. F. ^[1] ; Coletta-Yudice, E. D. ^[1] ; Nogueira, F. M. ^[1] ; De Sousa, M. B. Nering ^[1] ; Hayashi, M. A. ^[1] ; Lima-Landman, M. T. R. ^[1] ; Lapa, A. J. ^{[1, 2]} ; Souccar, C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Sect Nat Prod, Dept Pharmacol, BR-04044020 Sao Paulo - Brazil

^[2] Amazon Biotechnol Ctr, Lab Pharmacol & Toxicol, Manaus, Amazonas - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neuroscience; v. 269, p. 173-183, JUN 6 2014.
• Citações Web of Science: 9

Resumo

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 Ltd. All rights reserved. (AU)

• Processo FAPESP: 10/51344-3 - Mecanismos presinapticos envolvidos na liberação dos neurotransmissores colinérgico e GABAérgico no sistema nervoso central do camundongo mdx: análise da modulação nicotínica em animais
• Beneficiário: Caden Souccar
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/02536-4 - Transmissão colinérgica no sistema nervoso central do camundongo distrófico (MDX): análises das propriedades ligantes dos receptores nicotínicos neuronais e de seus efeitos modulatórios pré-sinápticos
• Beneficiário: Caden Souccar
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/56023-0 - Transmissao colinergica no sistema nervoso central do camundongo distrofico (mdx). estudo da liberacao de neurotransmissores e sua modulacao por recpetores nicotinicos
• Beneficiário: Eliana Della Coletta Yudice
• Modalidade de apoio: Bolsas no Brasil - Mestrado