RESUMEN
Oxidative damage of biomolecules increases with age and is postulated to be a major causal factor of various neurodegenerative disorders. Consequently, the concept of neuroprotection by antioxidants has been developed. Recently we have shown that the behaviour of young senescent-accelerated OXYS rats is similar to the behaviour of old Wistar animals. To determine the role of oxidative stress in this phenomenon we investigated age-related changes in protein carbonyls (PrC), lipid peroxides (LP), reduced glutathione (GSH), alpha-tocopherol (TP) and SOD activity in the brain of OXYS and Wistar rats. We also studied the effect of long-term supplementation with bilberry extract (2g/kg of diet) and Vitamin E (140 mg/kg of diet) on oxidative stress markers and on learning in passive avoidance test. In both rat strains LP, PrC and TP increased with age and at 24 months PrC was significantly higher (p<0.0001) in OXYS rats. At 3 months GSH was higher and SOD activity was lower in OXYS rats than in Wistar rats. SOD activity decreased with age in OXYS whereas increased in Wistar rats. Cognitive impairments in OXYS rats were manifested earlier than significant differences in the level of brain oxidative stress markers between two strains. By contrast, differences in antioxidant systems of Wistar and OXYS rats were registered at 3 months. Antioxidants attenuated cognitive deficits in OXYS rats, providing evidence for therapeutic role of antioxidants. Nevertheless, the exact mechanisms of neuroprotective effects of antioxidants in vivo and the real impact of oxidative stress on the development of cognitive impairments in OXYS rats still needs to be further investigated.
Asunto(s)
Envejecimiento/efectos de los fármacos , Antioxidantes/administración & dosificación , Trastornos del Conocimiento/dietoterapia , Suplementos Dietéticos , Estrés Oxidativo/efectos de los fármacos , Factores de Edad , Envejecimiento/fisiología , Análisis de Varianza , Animales , Reacción de Prevención/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Química Encefálica/efectos de los fármacos , Química Encefálica/fisiología , Glutatión/metabolismo , Masculino , Pruebas Neuropsicológicas , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Endogámicas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Vitamina E/metabolismoRESUMEN
After stress (immobilization in cages) plasma corticosterone level in prematurely aging OXYS rats was higher, while the content of NO metabolites was much lower than in Wistar rats. Stress increased blood pressure in OXYS and Wistar rats, the maximum values were observed in control and stressed OXYS rats. The concentration of reduced glutathione in the brain of OXYS rats was lower than in Wistar rats. After immobilization the concentration of reduced glutathione decreased in animals of both strains. The concentration of oxidized protein increased by 1.5 times only in OXYS rats. SOD activity remained unchanged, but in OXYS rats this parameter was higher than in Wistar rats. It can be hypothesized that high blood pressure, low NO content, high corticosterone concentration, and stress-induced deficiency of the antioxidant system (or combined effects of these factors) contribute to the development of neurodegenerative changes in the brain of OXYS rats.
Asunto(s)
Envejecimiento/metabolismo , Enfermedades Neurodegenerativas/fisiopatología , Estrés Fisiológico/fisiopatología , Animales , Encéfalo/metabolismo , Corticosterona/sangre , Glutatión/metabolismo , Inmovilización , Óxidos de Nitrógeno/sangre , Ratas , Ratas Wistar , Estrés Fisiológico/sangreRESUMEN
We analyzed the content of LPO products in various brain areas of Wistar and OXYS rats characterized by early appearance of changes in the emotional and cognitive spheres typical of aging. Marked differences between brain regions were found in both strains, but were more pronounced in Wistar rats. The content of LPO products in OXYS rats was higher in the midbrain, hippocampus, nuclei accumbens and striatum at the age of 2 months and in the midbrain, hippocampus, and nuclei accumbens at the age of 18 months. At the age of 18 months the content of LPO products was higher than at the age of 2 months in the amygdala and nuclei abbumbens of Wistar rats and in the nuclei accumbens and midbrain of OXYS rats, while in the hippocampus and hypothalamus of both rat strains and in the striatum of OXYS rats the content of LPO products at the age of 18 months was lower than at the age of 2 months. These results indicate that deviations in cognitive and emotional spheres of OXYS rats develop against the background of LPO activation in brain structures critical for training and memory, which indicates their relationship with oxidative stress.