RESUMEN
Rats were randomly assigned to enriched (EE) or standard environments (SE) at 21 or 73 days of age, for 17 days. Half of the rats of each rearing condition were trained in a radial maze (RM). At 38 days (pre-pubertal) or 90 days (young), rats were sacrificed and brain cytosolic and mitochondrial nitric oxide synthase (mtNOS) activity was assayed. Western blot analysis of brain mtNOS was conducted. In the pre-pubertal group, EE rats improved their performance in the RM while SE rats did not. In the young group, SE and EE rats showed a random performance in the RM. In SE pre-pubertal rats, training increased brain cytosolic NOS and mtNOS activity by 68% and 82%. In EE non-trained pre-pubertal rats, brain cytosolic NOS and mtNOS activity increased by 80% and 60%, as compared with SE non-trained pre-pubertal rats. In EE pre-pubertal rats that were trained, brain cytosolic NOS and mtNOS activity increased by 70% and 90%, as compared with SE pre-pubertal rats that were not trained. A higher protein expression of brain mtNOS was found in EE rats, as compared with SE animals. Mitochondrial complex I activity was higher in EE than in SE rats. Training had no effect on complex I activity neither in SE nor in EE rats. In young rats, no significant differences in enzyme activities were found between EE and SE rats. These results support the hypothesis that brief exposure to EE and training produce effects on behavioral performance and on biochemical parameters in an age-dependent manner.
Asunto(s)
Encéfalo/enzimología , Cognición/fisiología , Ambiente , Regulación Enzimológica de la Expresión Génica/fisiología , Óxido Nítrico Sintasa/metabolismo , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Conducta Animal , Complejo I de Transporte de Electrón/metabolismo , Masculino , Aprendizaje por Laberinto/fisiología , Mitocondrias/enzimología , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
In aged rodents, neuronal plasticity decreases while spatial learning and working memory (WM) deficits increase. As it is well known, rats reared in enriched environments (EE) show better cognitive performances and an increased neuronal plasticity than rats reared in standard environments (SE). We hypothesized that EE could preserve the aged animals from cognitive impairment through NO dependent mechanisms of neuronal plasticity. WM performance and plasticity were measured in 27-month-old rats from EE and SE. EE animals showed a better spatial WM performance (66% increase) than SE ones. Cytosolic NOS activity was 128 and 155% higher in EE male and female rats, respectively. Mitochondrial NOS activity and expression were also significantly higher in EE male and female rats. Mitochondrial NOS protein expression was higher in brain submitochondrial membranes from EE reared rats. Complex I activity was 70-80% increased in EE as compared to SE rats. A significant increase in the area of NADPH-d reactive neurons was observed in the parietotemporal cortex and CA1 hippocampal region of EE animals.
Asunto(s)
Envejecimiento , Trastornos del Conocimiento/prevención & control , Ambiente , Plasticidad Neuronal/fisiología , Óxido Nítrico/metabolismo , Conducta Espacial/fisiología , Análisis de Varianza , Animales , Western Blotting/métodos , Encéfalo/citología , Encéfalo/metabolismo , Recuento de Células/métodos , Diagnóstico por Imagen , Femenino , Inmunohistoquímica/métodos , Mediciones Luminiscentes/métodos , Masculino , Aprendizaje por Laberinto/fisiología , Memoria a Corto Plazo/fisiología , Mitocondrias/metabolismo , NADP/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Previous results have shown that inhibition of the renin-angiotensin system (RAS) either with an angiotensin II (Ang II), type 1 receptor blocker (losartan) or with an angiotensin converting enzyme inhibitor (ACEI, enalapril) has a protective effect on cardiovascular, renal, hepatic and cerebral structure and function during aging. The present study has analyzed the effect of chronic administration of a newly developed compound, omapatrilat, on clinical, histological and biochemical changes due to aging. Omapatrilat combines the action of an ACEI and of an inhibitor of a neutral endopeptidase involved in the metabolism of the atrial natriuretic peptide. The final effect is a decrease of a vasoconstrictor and proinflammatory mechanism like the RAS and the potentiation of two vasodilating compounds like bradykinin and the atrial natriuretic peptide. Based on these actions, its protective effect might be greater than formerly used pharmacological agents. Determinations have been performed on young adults (6 months old), adults (12 months old) or senile (18 months old) rats. Omapatrilat (35 mg/kg/day during 6 months and 20 mg/kg/day thereafter) was administered in the drinking water since weaning until sacrifice. Cardiovascular, renal, and cerebral structure as well as cognitive behavior, cardiovascular and renal function has been analyzed. The biochemical analysis has also established whether the beneficial action of Ang II inhibition is related to an increased activity of the nitric oxide synthase as observed in previous studies. Moreover, this study has tried to determine the relationship between the protective effect of these drugs and the levels of antioxidant defenses present in the blood and/or in the tissues. Hence, enzymatic and non-enzymatic antioxidants have been evaluated.