Age-related alterations of extracellular signal-regulated kinase 2 mRNA expression in the rat brain

Brain glutathione system (Glut-Syst) exhibits functional changes with age as well as during neurodegenerative diseases. After NGF treatment, cognitive functions and Glut-Syst activity are favorably modified in aged rats. also, the environmental enrichment (E-E) activates molecular mechanisms linked to cognition and sensorimotor coordination. We evaluate the functional repercussion of the combination of both factors. Old cognitively impaired rats received intracerebroventricular infusion of NGF (ICV, 22 mg/mL) or intraparenquimal (IP-nbM, 5.5 mg/mL) during 14 days using ALZET osmotic minipumps. Simultaneously, these animals received a passive training in an E-E during 4 weeks. A control group received training + saline infusion. Animals were assessed in the water maze task, avoidance passive test, open field test and transverse bridges test. At the end of the week 4, glutathione content and Choline Acetyltransferase (ChAT) activity were measured in brain areas of interest. E-E or NGF treatments, particularly the IP route, improve the rat's overall behavioral performance but a synergic effect was observed when NGF and E-E were applied simultaneously. A trend to hyperactivity was detected in the ICV group. Glutathione content and ChAT activity exhibited significant changes according to the group and brain area. It's well known that activity/levels of antioxidant enzymes and ChAT activity are related to age, brain region and neurotrophins activity. Results point out the possibilities of neurotrophic therapy if an adequate route of delivery is used as well as the benefit of combining a neurorehabilitation program on both, behavioural and protection from oxidative stress.