Estudo do sistema purinérgico e colinérgico no encéfalo de animais submetidos à hipoperfusão encefálica crônica e ao ambiente enriquecido

Abstract

Chronic cerebral hypoperfusion (CCH) has frequently been associated with neurodegenerative diseases. A persistent reduction of cerebral blood flow (CBF) changes the neuronal homeostasis causing diffuse ischemic damage and activating various systems, including the purinergic and cholinergic systems. Extracellular nucleotides ATP, ADP, AMP and adenosine nucleoside are important signaling molecules in the central nervous system (CNS). Their extracellular levels are controlled by the action of an enzyme complex formed by the enzymes E-NTPDase, E-5'nucleotidase and E-ADA. The enzyme acetylcholinesterase (AChE) plays an essential role in cholinergic mechanism also can act as an inflammatory marker. The enriched environment (EE), to promote hippocampal neurogenesis and synaptic plasticity seems to have neuroprotective effect on commitments related to aging. Thus, the aim of this study was to evaluate the influence of EE using the experimental model of HEC by occluding two vessels (2VO) in the activity of the enzymes AChE and purinergic system. Male Wistar rats (200-250g) (n = 40) were divided into 4 groups, two of them exposed to the EE 30 days and the other groups housed in standard environment (SE). The groups were named as: 2VO/EE (n = 12), sham/EE (n = 8), 2VO/SE (n = 12) and sham/SE (n = 8). The results showed an increase in E-NTPDase enzyme activity in the hydrolysis of ATP in 2VO/EE and 2VO/SE groups in the cortex synaptosomes and 2VO/EE group hippocampus when compared to their respective controls. Also an increase in the hydrolysis of ADP in synaptosomes in the cortex of 2VO/SE group and hippocampal 2VO/EE group. As for E-5'-NT enzyme activity was observed a significant increase in 2VO/EE and 2VO/SE groups. However, there is a less pronounced increase in AMP hydrolysis in the hippocampus of animals 2VO/EE relative to 2VO/SE. When we evaluated the activity of E-ADA, no statistical difference was observed in 2VO groups compared to their controls. The activity of AChE enzyme increased in the cortex synaptosomes in 2VO/EE and hippocampal 2VO/SE group. The results suggest that the damage caused by HEC in chronic phase leading to increased adenosine levels in the extracellular space and the EE exposure, especially in the hippocampus, can reduce AMP hydrolysis. Additionally the activity of AChE enzyme increased in hypoperfused rats. Thus, conclude that chronic hypoperfusion alters the activity of the enzymes of the purinergic and cholinergic system and the EE may have an adjuvant effect on neuroprotection.