RESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there are few therapeutic regimens that influence the underlying pathogenic phenotypes. However, of the currently available therapies, exercise training is considered to be one of the best candidates for amelioration of the pathological phenotypes of AD. Therefore, we directly investigated exercise training to determine whether it was able to ameliorate the molecular pathogenic phenotypes in the brain using a neuron-specific enolase (NSE)/Swedish mutation of amyloid precursor protein (APPsw) transgenic (Tg) mice as a novel AD model. To accomplish this, Non-Tg and NSE/ APPsw Tg mice were subjected to exercise on a treadmill for 16 weeks, after which their brains were evaluated to determine whether any changes in the pathological phenotype-related factors had occurred. The results indicated (i) that amyloid beta-42 (Abeta-42) peptides were significantly decreased in the NSE/APPsw Tg mice following exercise training; (ii) that exercise training inhibited the apoptotic biochemical cascades, including cytochrome c, caspase-9, caspase-3 and Bax; (iii) that the glucose transporter-1 (GLUT-1) and brain-derived neurotrophic factor (BDNF) proteins induced by exercise training protected the neurons from injury by inducing the concomitant expression of genes that encode proteins such as superoxide dismutase-1 (SOD-1), catalase and Bcl-2, which suppress oxidative stress and excitotoxic injury; (iv) that heat-shock protein-70 (HSP-70) and glucose-regulated protein-78 (GRP-78) were significantly increased in the exercise (EXE) group when compared to the sedentary (SED) group, and that these proteins may benefit the brain by making it more resistant to stress-induced neuron cell damage; (v) and that exercise training contributed to the restoration of normal levels of serum total cholesterol, insulin and glucose. Taken together, these results suggest that exercise training represents a practical therapeutic strategy for human subjects suffering from AD. Moreover, this training has the potential for use in new therapeutic strategies for the treatment of other chronic disease including diabetes, cardiovascular and Parkinson's disease.
Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/terapia , Precursor de Proteína beta-Amiloide/metabolismo , Fosfopiruvato Hidratase/metabolismo , Condicionamento Físico Animal , Doença de Alzheimer/enzimologia , Peptídeos beta-Amiloides/metabolismo , Animais , Comportamento Animal , Encéfalo/enzimologia , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Caspases/metabolismo , Citocromos c/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Chaperona BiP do Retículo Endoplasmático , Ativação Enzimática , Transportador de Glucose Tipo 1/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico , Humanos , Camundongos , Camundongos Transgênicos , Chaperonas Moleculares , Fragmentos de Peptídeos/metabolismo , Fenótipo , Superóxido Dismutase/metabolismo , Regulação para Cima , Proteína X Associada a bcl-2/metabolismoRESUMO
Selenoprotein is associated with a variety of serious diseases, including infectious diseases, neurodegenerative disorders, cancer and cardiovascular disease. The aim of this study was to produce a new transgenic (Tg) rat expressing human selenoprotein M (SelM) in order to examine the protective function of the antioxidant status in vivo. To achieve this, a new lineage of Tg rats was produced by the microinjection of pCMV/GFP-hSelM constructs into a fertilized rat egg. Several conclusions can be drawn based on the results of the present study. The human SelM gene was successfully expressed at both the transcription and protein levels in the CMV/GFP-hSelM Tg rats. This Tg rat showed a different enzyme activity for the antioxidant protein in the various tissues examined. In response to the 2,2'-azobiz(2-amidinopropane) dihydrochloride (AAPH) injection, the Tg rats showed a lower level of antioxidant and H2O2 concentration as the activity of the antioxidant enzyme was maintained at a higher level in the Tg rats than in the non-Tg rats. Also, the neutrophil-to-lymphocyte ratio was significantly increased in this Tg rat, even though the level of corticosterone remained unchanged in both genotypes. Thus, the results of this study demonstrated that the CMV/GFP-hSelM Tg rat can serve as an animal model for the maintenance of a high level of antioxidant status and can be used to study the biological function of selenoprotein in infectious diseases, cardiovascular disease and cancer.
Assuntos
Antioxidantes/metabolismo , Expressão Gênica , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/metabolismo , Leucócitos/citologia , Selenoproteínas/genética , Superóxido Dismutase/metabolismo , Animais , Animais Geneticamente Modificados , Corticosterona/metabolismo , Citomegalovirus , Modelos Animais de Doenças , Eritrócitos/enzimologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Vetores Genéticos , Proteínas de Fluorescência Verde/metabolismo , Humanos , Peróxido de Hidrogênio/sangue , Especificidade de Órgãos , Ratos , Ratos Sprague-Dawley , Selenoproteínas/metabolismoRESUMO
Transportation can cause stress to laboratory animals and alter physiological characteristics that may confound experimental results. The authors investigated stress-related effects of 3-4 h of transportation by truck in two strains of mice (C57BL/6, which are known to be aggressive, and ICR, which are less aggressive). Transported mice had sufficient space and access to water, though temperature in the truck was lower than what is usually recommended. Transportation affected the following parameters in both strains of mice: (i) serum corticosterone concentrations, (ii) expression of the chaperone proteins Hsp70 and Grp78 in various tissues and (iii) concentrations of serological enzymes that are associated with liver disease. These parameters also differed substantially between the two strains of mice.
Assuntos
Criação de Animais Domésticos , Temperatura Baixa/efeitos adversos , Meio Ambiente , Estresse Psicológico/sangue , Animais , Comportamento Animal , Corticosterona/sangue , Chaperona BiP do Retículo Endoplasmático , Enzimas/sangue , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Chaperonas Moleculares/metabolismo , Estresse Psicológico/fisiopatologia , Fatores de Tempo , Meios de TransporteRESUMO
The present study was designed to define how dietary fat type regulates body adiposity in dietary obesity-susceptible (DOS) Sprague-Dawley (SD) rats. Eighty-three SD rats received a purified diet containing 50 g maize oil (MO)/kg for 3 weeks and then thirty-nine of the rats, designated as the DOS rats, were allotted to diets containing 160 g MO (DOS-MO), beef tallow (DOS-BT) or fish oil (DOS-FO)/kg for 9 weeks. As a result of the experiment, the DOS-FO rats had significantly (P<0.05) reduced weight gain and abdominal and epididymal fat-pad mass than the DOS-MO and DOS-BT rats. Serum leptin level was also significantly (P<0.05) lower in the DOS-FO rats; however, hypothalamic leptin receptor (a and b) mRNA and neuropeptide Y expressions were not altered by dietary fat sources. A lower acetyl-CoA carboxylase mRNA expression in the liver was observed in the DOS-FO group, whereas hepatic peroxisome proliferator-activated receptor-gamma mRNA and protein expressions were markedly elevated in the DOS-FO group compared with those in the other groups. We did not observe differences in acetyl-CoA carboxylase and peroxisome proliferator-activated receptor-gamma expressions in epididymal fat of the DOS rats consuming MO, BT or FO. It is concluded from our present observations that dietary fat type, especially that rich in FO, plays a potential role in down-regulation of adiposity by altering hepatic lipogenic genes, rather than feeding behaviour, in the DOS-SD rats.