Possible involvement of PI3K/AKT/mTOR signaling pathway in the protective effect of selegiline (deprenyl) against memory impairment following ischemia reperfusion in rat

• Published in: Neuropeptides (Edinburgh) 2019-10, Vol.77, p.101942-101942, Article 101942
• Main Authors: Amini-Khoei, Hossein, Saghaei, Elham, Mobini, Gholam-Reza, Sabzevary-Ghahfarokhi, Milad, Ahmadi, Reza, Bagheri, Nader, Mokhtari, Tahmineh
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animal behavior; Animals; Brain Ischemia - complications; Brain Ischemia - metabolism; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Immunohistochemistry; Ischemia; Male; Maze Learning - drug effects; Memory; Memory - drug effects; Memory Disorders - drug therapy; Memory Disorders - etiology; Memory Disorders - metabolism; Neurons; Neurons - drug effects; Neurons - metabolism; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT/mTOR signaling; Proto-Oncogene Proteins c-akt - metabolism; Rat; Rats; Rats, Sprague-Dawley; Reperfusion; Rodents; Selegiline; Selegiline - pharmacology; Selegiline - therapeutic use; Signal transduction; Signal Transduction - drug effects; Spatial memory; TOR protein; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0143-4179; 1532-2785
• DOI: 10.1016/j.npep.2019.101942

Short-term cerebral ischemia led to memory dysfunction. There is a pressing need to introduce effective agents to reduce complications of the ischemia. Involvement of PI3K/AKT/mTOR signaling pathway has been determined in the neuroprotective effect of various agents. Selegiline (deprenyl) possessed neuroprotective properties. In this study global ischemia/reperfusion was established in rats. Selegiline (5 mg/kg for 7 consecutive days) administrated via intraperitoneal route. Possible involvement of PI3K/AKT/mTOR signaling pathway was evaluated using qRT-PCR, immunohistochemistry and histophatologic evaluations in the hippocampus. Spatial memory was evaluated by morris water maze (MWM). Results showed that ischemia impaired the memory and ischemic rats spent more time to find hidden platform in the MWM. Ischemia significantly decreased levels of PI3K, AKT and mTOR in the hippocampus. Histopathologic assessment revealed that the percent of dark neurons significantly increased in the CA1 area of the hippocampus of ischemic rats. Selegiline improved the memory as ischemic rats spent fewer time to find hidden platform in the MWM. Findings showed that selegiline increased the level and expression of PI3K, AKT and mTOR as well as decreased the proportion of dark neurons in the CA1 area of the pyramidal layer of the hippocampus. We concluded that selegiline, partially at least, through increases the expression of PI3K, AKT and mTOR as well as decreases the percent of dark neurons in the hippocampus could improve the memory impairment following the ischemia in rats. •Ischemia led to memory dysfunction in rats.•Ischemia reduced the level of AKT, PI3K, mTOR and p-mTOR.•Ischemia increased the percent of dark (dead) neurons in the hippocampus.•Selegiline reversed the negative effect of ischemia on the memory function.•Selegiline increased the level of AKT, PI3K, mTOR and p-mTOR and decreased the number of dark neurons.