RESUMO
AIMS: In this study, we evaluated the ability of differentiating embryonic chick DRG neurons to release and respond to acetylcholine (ACh). In particular, we investigated the neuronal soma and neurites as sites of ACh release, as well as the mechanism(s) underlying this release. MAIN METHODS: ACh release from DRG explants in the Campenot chambers was measured by a chemiluminescent assay. Real-time PCR analysis was used to evaluate the expression of ChAT, VAChT, mediatophore and muscarinic receptor subtypes in DRGs at different developmental stages. KEY FINDINGS: We found that ACh is released both within the central and lateral compartments of the Campenot chambers, indicating that ACh might be released from both the neuronal soma and fibers. Moreover, we observed that the expression of the ChAT and mediatophore increases during sensory neuron differentiation and during the post-hatching period, whereas VAChT expression decreases throughout development. Lastly, the kinetics of the m2 and m3 transcripts appeared to change differentially compared to the m4 transcript during the same developmental period. SIGNIFICANCE: The data obtained demonstrate that the DRG sensory neurons are able to release ACh and to respond to ACh stimulation. ACh is released both by the soma and neurite compartments. The contribution of the mediatophore to ACh release appears to be more significant than that of VAChT, suggesting that the non-vesicular release of ACh might represent the preferential mechanism of ACh release in DRG neurons and possibly in non-cholinergic systems.
Assuntos
Acetilcolina/metabolismo , Embrião de Galinha/citologia , Embrião de Galinha/embriologia , Neurogênese , Neurônios/citologia , Animais , Células Cultivadas , Embrião de Galinha/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Fatores de Crescimento Neural/genética , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores Muscarínicos/genética , Proteínas Vesiculares de Transporte de Acetilcolina/genéticaRESUMO
Pharmacological interventions that increase myofiber size counter the functional decline of dystrophic muscles. We show that deacetylase inhibitors increase the size of myofibers in dystrophin-deficient (MDX) and alpha-sarcoglycan (alpha-SG)-deficient mice by inducing the expression of the myostatin antagonist follistatin in satellite cells. Deacetylase inhibitor treatment conferred on dystrophic muscles resistance to contraction-coupled degeneration and alleviated both morphological and functional consequences of the primary genetic defect. These results provide a rationale for using deacetylase inhibitors in the pharmacological therapy of muscular dystrophies.
