RESUMO
Assisted-treadmill training, may be helpful in promoting muscle mass preservation after incomplete spinal cord injury (SCI). However, biological mechanism involved in this process is still not fully understood. This study investigated the effects of locomotor treadmill training on muscle trophism mediated by protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) in paraplegic rats. Adult female Wistar rats underwent an incomplete thoracic SCI induced by compression using an aneurysm clip. After 7 days, injured animals started a 3-week locomotor treadmill training with body weight-support and manual step help. Soleus trophism was measured by muscle weight and transverse myofiber cross-sectional area (CSA). An enzyme-linked immunosorbent assay (ELISA) and western blot analysis were used to detect brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), Akt, mTOR and p70S6K in paretic soleus. Trained animals did not show locomotor improved, but present an increase in muscle weight and myofiber CSA. Furthermore, the levels of Akt, p70S6K phosphorylation, mTOR and TrkB receptor were increased by training in soleus. In contrast, muscle BDNF levels were significantly reduced after training. The results suggest locomotor treadmill training partially reverts/prevents soleus muscle hypotrophy in rats with SCI. Furthermore, this study provided the first evidence that morphological muscle changes were caused by Akt/mTOR/p70S6K signaling pathway and TrkB up-regulation, which may increase the sensitivity of muscle, reducing autocrine signaling pathway demand of BDNF for cell growth.
Assuntos
Teste de Esforço/métodos , Locomoção/fisiologia , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Paraplegia/metabolismo , Serina-Treonina Quinases TOR/biossíntese , Animais , Feminino , Músculo Esquelético/patologia , Atrofia Muscular/patologia , Atrofia Muscular/prevenção & controle , Paraplegia/patologia , Paraplegia/reabilitação , Ratos , Ratos WistarRESUMO
AIM: To systematically review studies that investigated the basal metabolic rate (BMR) and resting metabolic rate (RMR) of physically disabled adult subjects. METHODS: The studies were identified via MedLine, Science Direct, Science Search, Scientific Electronic Library Online, Wiley, Latin American and Caribbean Health Sciences Literature, Cochrane, Indice Bibliográfico Espanõl de Ciencias de la Salud, Scopus, ProQuest Dissertations & Theses Database and System for Information on Grey Literature in Europe. No restriction on publication date was imposed. RESULTS: Data from 6 studies were included. The results showed that physically disabled adult subjects have a lower BMR and/or RMR compared to nondisabled subjects. However, the difference between the groups disappeared when the BMR and RMR were adjusted for fat-free mass. Due to the small number of studies on this subject and the limited types of physical disabilities evaluated in the literature, we could not make a definitive conclusion. CONCLUSIONS: Disabled individuals seem to have a lower absolute BMR and/or RMR than able-bodied adults; however, this difference was not present or else it disappeared in half of the studies, after adjusting for body mass and/or fat-free mass.
Assuntos
Metabolismo Basal , Pessoas com Deficiência , Paraplegia/metabolismo , Adulto , Composição Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND/AIM: Chagas' disease is caused by Trypanosoma cruzi and occurs in most Latin American countries. The protozoan may colonize the central nervous system (CNS) of immune-compromised human hosts, thus causing neuronal disorders. Systemic control of the intracellular forms of the parasite greatly depends on the establishment of a TH1 response and subsequent nitric oxide (NO) release. At the CNS, it is known that low concentrations of NO promote neuronal survival and growth, while high concentrations exert toxic effects and neuron death. Accounting for NO production by astrocytes is the glia-derived factor S100beta, which is overproduced in some neurodegenerative diseases. In the current work, we studied the expression of NO, interferon (IFN)-gamma and S100beta in the spinal cord tissue of IL-12p40KO mice infected with T. cruzi, a model of neurodegenerative process. METHODS: IL-12p40KO and wild-type (WT) female mice infected with T. cruzi Sylvio X10/4 (10(5) trypomastigotes, intraperitoneally) were euthanized when IL-12p40KO individuals presented limb paralysis. Spinal cord sections were submitted to immunohistochemical procedures for localization of neurofilament, laminin, nitrotyrosine, NO synthases (NOS), IFN-gamma and S100beta. The total number of neurons was estimated by stereological analysis and the area and intensity of immunoreactivities were assessed by microdensitometric/morphometric image analysis. RESULTS: No lesion was found in the spinal cord sections of WT mice, while morphological disarrangements, many inflammatory foci, enlarged vessels, amastigote nests and dying neurons were seen at various levels of IL-12p40KO spinal cord. Compared to WT mice, IL-12p40KO mice presented a decrement on total number of neurons (46.4%, p < 0.05) and showed increased values of immunoreactive area for nitrotyrosine (239%, p < 0.01) and NOS (544%, p < 0.001). Moreover, the intensity of nitrotyrosine (16%, p < 0.01), NOS (38%, p < 0.05) and S100beta (21%, p < 0.001) immunoreactivities were also augmented. No IFN-gamma-labeled cells were seen in WT spinal cord tissue, contrary to IL-12p40KO tissue that displayed inflammatory infiltrating cells and also some parenchymal cells positively labeled. CONCLUSION: We suggest that overproduction of NO may account for neuronal death at the spinal cord of T. cruzi-infected IL-12p40KO mice and that IFN-gamma and S100beta may contribute to NOS activation in the absence of IL-12.
Assuntos
Subunidade p40 da Interleucina-12/genética , Mielite/metabolismo , Degeneração Neural/metabolismo , Óxido Nítrico/biossíntese , Medula Espinal/metabolismo , Trypanosoma cruzi/metabolismo , Animais , Células Cultivadas , Doença de Chagas/metabolismo , Doença de Chagas/fisiopatologia , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Parasita , Imunidade Inata/imunologia , Mediadores da Inflamação/metabolismo , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mielite/parasitologia , Mielite/fisiopatologia , Degeneração Neural/parasitologia , Degeneração Neural/fisiopatologia , Fatores de Crescimento Neural/metabolismo , Neurônios/metabolismo , Neurônios/parasitologia , Neurônios/patologia , Óxido Nítrico Sintase Tipo I/metabolismo , Paraplegia/metabolismo , Paraplegia/parasitologia , Paraplegia/fisiopatologia , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/metabolismo , Medula Espinal/parasitologia , Medula Espinal/fisiopatologia , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
The autosomal dominant hereditary spastic paraplegias (AD-HSP) are a heterogeneous group of degenerative disorders of the central motor system, characterized by progressive spasticity of the lower limbs. Five loci for pure AD-HSP have been identified to date: SPG3 at 14q, SPG4 at 2p, SPG6 at 15q, SPG8 at 8q, and more recently SPG10 at 12q. We have analyzed a Brazilian family with 16 affected individuals by pure AD-HSP who developed progressive gait disturbance with onset at age 18-26 years. Linkage analysis performed with 13 relatives (6 affected and 7 normal) excluded SPG3, SPG4, and SPG6 as candidate regions. However, positive LOD scores were obtained with markers flanking the candidate region for the SPG8 locus [maximum two point Lod score (Zmax) = 3.3 at theta = 0 for D8S1804]. In this region lies the syntrophin beta 1 gene (SNT2B1), a widely expressed dystrophin-associated protein and therefore a good positional and functional candidate for this disease. Immunohistochemical and Western Blot (WB) studies showed that the distribution, expression, and apparent molecular weight of the beta 1 syntrophin protein were comparable to those of normal control individuals. Therefore, it is unlikely that defects in this protein are related to SPG8, at least in the present family.