Effects of CF102, an Adenosine A3 Receptors Agonist, on Memory Deficits and Oxidative Stress in a Mouse Model of Streptozotocin‐Induced Dementia of Alzheimer's Type

Abstract

Alzheimer's disease (AD) is an age‐related neurodegenerative disease characterized by a progressive decline in cognitive functions. Adenosine receptors play a pivotal role in disease progression, however, adenosine A3 receptors are understudied and their effects vastly unknown. We now investigated the effects of the activation of adenosine A3 receptors on memory deficits and oxidative damage in a mouse model of streptozotocin‐induced experimental dementia of Alzheimer's type. Male Swiss mice received bilateral intracerebroventricular injections of streptozotocin (STZ, 3 mg/kg) dissolved in artificial cerebrospinal fluid. Two days after the first STZ administration, injections were repeated, and the animals were treated with the A3 receptor agonist, CF102 (200 μg/kg intraperitoneally), or vehicle (2% DMSO in saline), 1 h after surgery and once a day until the last day of behavioral evaluation (18th after the first STZ injection). The animals subjected to STZ administration showed significant recognition memory deficits evaluated by the object recognition task, spatial memory deficits evaluated by water maze test, and early and late memory deficits in the passive avoidance test. No differences of locomotor activity in the open field test were observed between groups. STZ also increased malonaldehyde and nitrite contents in the hippocampus. The treatment with CF102 significantly prevented the early and late memory deficits and object recognition memory deficits. CF102 treatment also reduced the increase of nitrite production in 37% in the hippocampus when compared to STZ group. These data highlight the therapeutic potential of A3 agonists in AD, however the role of these receptors on STZ‐induced AD model requires more investigation.Support or Funding InformationSupported by Brazilian National Research and Development Council (CNPq), Coordination for the Improvement of Higher Education Personnel (CAPES) ‐ Brazil, and the Research Support Foundation of Ceará (FUNCAP) – Brazil.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.