Inosina como um agente neuroprotetor em modelos experimentais para a Doença de Alzheimer

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease and the main cause of dementia in the elderly. Regarding the pathophysiological mechanisms involved in AD, we can highlight the cholinergic deficit, oxidative stress, neuroinflammation and changes in purinergic signaling. Considering that the drugs available for AD only relieve symptoms, the search for more effective therapies becomes important. Inosine is an endogenous purine that has antioxidant, anti-inflammatory and neuroprotective actions. Thus, the objective of this work was to investigate the effects of this purine on memory and on neurochemical parameters in experimental models of AD. Two protocols were evaluated: in the first, the rats were divided into the following groups: control, scopolamine (SCO), SCO + inosine (50 mg / kg) and SCO + inosine (100 mg / kg). Inosine was pre-administered for 7 days, intraperitoneally. On the eighth day, SCO was administered pre- or post-training for the inhibitory avoidance task. In the second, the rats were divided into groups: control, streptozotocin (STZ), STZ + inosine (50 mg / kg) and STZ + inosine (100 mg / kg). STZ was administered by intracerebroventricular injection and the animals were treated with inosine for 25 days. In both protocols, inosine was able to prevent memory deficits, changes in cholinergic enzymes and oxidative stress in the cerebral cortex and hippocampus. In the STZ- induced AD model, inosine was also able to decrease the A2A adenosine receptor immunoreactivity, increase the levels of anti-inflammatory cytokines and the expression of the brain-derived neurotrophic factor (BDNF) and its receptor (TrkB). The morphological changes induced by STZ in the hippocampus were also mitigated by treatment with inosine (50 and 100 mg / kg). The results obtained demonstrated that inosine affects multiple brain targets, suggesting that this nucleoside may have an important therapeutic potential against cognitive deficits and tissue damage associated with AD or other neurodegenerative diseases.