Mitochondrial function and nitric oxide production in hippocampus and cerebral cortex of rats exposed to enriched environment.

Male rats (21days) were assigned to enriched environment (EE) or to standard environment (SE) for 1year. Oxygen consumption and the sensitivity to calcium induced mitochondrial permeability transition (MPT), through mitochondrial membrane potential (DeltaPsi(m)) and swelling, were determined in isolated hippocampal and cerebral cortex mitochondria. Mitochondrial H(2)O(2) production rate, and NOS activity and expression associated with mitochondrial membranes were also assayed. Results showed that state 3 respiratory rate was increased by 80% in cerebral cortex mitochondria from EE rats and no changes were observed in hippocampal mitochondria after EE exposure. Calcium induced-swelling was 40% and 53% lower in hippocampal and cerebral cortex mitochondria from EE rats, as compared with SE rats. Calcium loading induced membrane depolarization in cerebral cortex mitochondria from EE rats but did not affect mitochondrial DeltaPsi(m) in hippocampal mitochondria from EE animals, probably due to decreased H(2)O(2) formation. NO production associated to mitochondrial membranes was increased by 195% in cerebral cortex mitochondria but decreased by 47% in hippocampal mitochondria from EE rats, as compared with SE rats. Western blot analysis from nNOS protein expression associated to mitochondrial samples revealed a similar pattern. Our results suggest that in hippocampus and cerebral cortex, EE exposure protects mitochondria against calcium-induced MPT maintaining a convenient membrane potential, which assures a continuous energy supply.

Exposure to enriched environments increases brain nitric oxide synthase and improves cognitive performance in prepubertal but not in young rats.

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.

Implicacion de la via colinergica muscarinica en la memoria de trabajo espacial / Implication of muscarinic cholinergic neurotransmissionon spatial working memory

Ratas macho de la cepa Wistar, entrenadas en una tarea de alternancia en un laberinto en T (memoria de trabajo) y en una discriminación de claves visuales y tactiles (memoria asociativa) fueron tratadas por vía sistémica, con dos bloqueantes de la neurotransmisión colinérgica muscarinica (escopolamina y atropina), en un rango de dosis entre 0,1 y 3,0 mg/kg. Ambos antagonistas colinergicos indujeron un aumento significativo de los errores (p < 0,05), aunque las dosis requeridas para ello fueron diferentes: 1,0 y 3,0 mg/kg para la atropina, y 0,6 y 1,0 mg/kg para la escopolamina. Estas diferencias podrian ser atribuidas, en primera instancia, a la mayor penetración de la escopolamina a través de la barrera hemato-encefálica. Ninguna de las dosis de atropina o escopolamina empleadas modificó significativamente la ejecución de la tarea de memoria asociativa. LaN-Metil-escopolamina, un análogo cuaternario de la escopolamina y por ende de menor penetración al SNC ante su administración sistémica, no produjo efectos significativos sobre el rendimiento en ninguna de las dos tareas. Ello sugiere que las acciones desarrolladas por la escopolamina y por extensión las observadas con atropina, son de naturaleza central. Finalmente se examina-ron tambien los posibles efectos de la manipulación de la demora y de la cantidad de recompensa, sobre el rendimiento en MT espacial.