RESUMO
Effects of previous strength training can be long-lived, even after prolonged subsequent inactivity, and retraining is facilitated by a previous training episode. Traditionally, such "muscle memory" has been attributed to neural factors in the absence of any identified local memory mechanism in the muscle tissue. We have used in vivo imaging techniques to study live myonuclei belonging to distinct muscle fibers and observe that new myonuclei are added before any major increase in size during overload. The old and newly acquired nuclei are retained during severe atrophy caused by subsequent denervation lasting for a considerable period of the animal's lifespan. The myonuclei seem to be protected from the high apoptotic activity found in inactive muscle tissue. A hypertrophy episode leading to a lasting elevated number of myonuclei retarded disuse atrophy, and the nuclei could serve as a cell biological substrate for such memory. Because the ability to create myonuclei is impaired in the elderly, individuals may benefit from strength training at an early age, and because anabolic steroids facilitate more myonuclei, nuclear permanency may also have implications for exclusion periods after a doping offense.
Assuntos
Núcleo Celular/ultraestrutura , Fibras Musculares Esqueléticas/fisiologia , Fibras Musculares Esqueléticas/ultraestrutura , Condicionamento Físico Animal/fisiologia , Animais , Apoptose , Feminino , Humanos , Hipertrofia , Masculino , Camundongos , Modelos Animais , Modelos Biológicos , Denervação Muscular , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Ratos , Ratos Wistar , Treinamento ResistidoRESUMO
AIM: Muscle is perhaps the most frequently considered tissue for non-viral gene therapy, in particular after gene transfer by electroporation. Expression in muscle is stable, but since the cell turnover is so slow incorporation in the host genome is not required. This raises interesting practical and theoretical questions related to the behaviour of the transgenic DNA under such conditions. METHODS: We have investigated expression of reporter genes from plasmid mixtures electroporated into the extensor digitorum longus (EDL) muscle in mice in order to assess the degree of coexpression. RESULTS: Under conditions where the reporter is easily identified the coexpression rate was 100%, as none of 287 fibres from five different muscles expressing blue fluorescent protein (BFP) failed to express green fluorescent protein (GFP). With other reporter combinations the rate was lower, but this we attribute to marginal sensitivity for fluorescent proteins, or from reporter protein degradation for beta-galactosidase. CONCLUSIONS: The high degree of coexpression suggests that a large copy number takes part in the final transcription with this system. The finding also enhances the usefulness of muscle and electroporation for gene therapy and experimental biology.