Adenosine ameliorated Aβ25−35-induced brain injury through the inhibition of apoptosis and oxidative stress via an ERα pathway

Abstract

Previous studies have shown that adenosine has estrogen-like activity mediated by estrogen receptor α (ERɑ). This study aimed to examine the effects of adenosine on Aβ25–35-induced brain injury and the underlying mechanisms involved. Adenosine (Ade, 20 mg/kg, i.g.) was administered for four weeks, followed by the induction of Alzheimer's disease (AD) by Aβ25–35 (200 µM, 3 µL/20 g, i.c.v.). Furthermore, a specific ERα blocker (MPP, 0.3 mg/kg, i.p.) was administered 30 min before the treatments of adenosine to evaluate whether the observed effects elicited by adenosine were mediated via ERα. In addition, the learning and memory ability, neuronal damage, and the levels of amyloid β-protein (Aβ), phosphorylated Tau Protein (p-Tau), apoptosis, oxidative stress, immune cells, and ERα were examined. The antagonistic effect of MPP (1 µM) against adenosine (5 µM) in Aβ25–35 (20 µM, 24 h)-induced N9 and PC-12 cells was also investigated. Adenosine improved learning and memory ability, reduced neuronal damage, downregulated Aβ42/Aβ40, p-Tau, apoptosis, and oxidative stress, transformed immune cells, and increased the expression of ERα following Aβ25–35 challenge. MPP could block these effects. Moreover, MPP also blocked the effects of adenosine on the levels of apoptosis and reactive oxygen species (ROS) in Aβ25–35-induced N9 and PC-12 cells. Adenosine ameliorated Aβ25–35-induced brain injury by inhibiting apoptosis and oxidative stress, possibly via an ERα pathway.