Estudo da interação do sistema purinérgico, colinérgico e funções cognitivas na demência esporádica do tipo alzheimer: os efeitos das antocianinas

Abstract

Dementia is a brain disorder characterized by decline in several mental functions and results in deficits in memory functioning in a variety of cognitive tasks. Evidence has emerged showing that anthocyanins (ANT) possess antioxidant, vasodilator and neuroprotective properties, and more recently are able to improve memory. The aim of our study was to investigate the role of ANT on memory and relate these changes to the cholinergic and purinergic in a model of amnesia induced by scopolamine (SCO), in a model of sporadic dementia of the Alzheimer type (SDAT), induced by intracerebroventricular injection of streptozotocin (ICV-STZ). We used male adult rats, which were previously treated with an extract rich in ANT (200mg/kg) for seven days. For each study protocol, we used the same dose of ANT only varying the time of drug administration SCO ip (1mg/kg) and ICV-STZ (3mg/kg) specific to the models of amnesia and dementia, respectively. The results showed that pretreatment with ANT reversed the memory deficits in an amnesia model and also in the model of SDAT. Regarding the activity of AChE enzyme was observed a significant increase in SCO group accompanied by a decrease in the activity of Na+, K+-ATPase and Ca2+-ATPase, and these effects were prevented by ANT treatment. It was also observed an increase in NTPDase activity, decreased in ADA and 5'-NT activity from brain of animals injected with SCO, accompanied by a reduction in the ATP and adenosine levels, which can compromise the purinergic signaling. ANT treatment was able to prevent changes in NTPDase, ADA and 5 -NT. The ICV-STZ treated animals showed a high anxiogenic-like behavior and ANT treatment prevented this effect, indicating that it can be seen with anxiolytic properties molecules, as in vitro experiments demonstrated their affinity for the benzodiazepine site of GABAA receptors. The animals ICV-STZ treated showed marked increase in AChE activity and Ca2+-ATPase, and decreased activity of Na+, K+-ATPase, causing disturbances in electrolyte concentrations of Na+ and Ca2+ and this could lead to neuronal excitotoxic and increased activity AChE in SDAT, and these effects were prevented by administration of ANT. Moreover, both the density and immunoreactivity for 5'-NT was markedly reduced in animals ICV-STZ as compared with the group of -normal rats. In addition, ICV-STZ treatment showed a significant decrease in 5'-NT and NTPDase activity in a model of SDAT. In the hippocampus of ICV-STZ animals was found considerable increase in levels of ROS total, MDA and NOx, indicating marked oxidative stress, which could lead to a decrease in neuronal viability and NTPDase and 5'-NT activity, since they are linked to the cell membrane. In this context, we suggest that both cholinergic and purinergic systems can be regulated by ANT treatment, thus defining use of this compound as a new strategy to control the deterioration of memory in aging associated with these systems.