ACA, an inhibitor phospholipases A2 and transient receptor potential melastatin-2 channels, attenuates okadaic acid induced neurodegeneration in rats

In recent studies, it has been shown that the Transient Receptor Potential Melastatin-2 Channels (TRPM2) and Phospholipases A2 (PLA 2 ) inhibitors may have a protective effect on neurons. This study was aimed to investigate the protective effect of TRPM2 and PLA 2 inhibitor N -( p -amylcinnamoyl) Anthranilic Acid (ACA) in a neurodegenerative model induced by Okadaic Acid (OKA). OKA (200 ng/10 μl) was administered bilateral intracerebroventricularly as a single injection. OKA-treated rats showed significant impairments of spatial memory in Morris Water Maze Test. OKA-induced memory-impaired rats showed increased numbers of degenerated neurons and Caspase-3, tau phosphorylated ser396, β-amyloid positive cells in the hippocampus and cerebral cortex. Furthermore, OKA-treated rats exhibited significantly increased MDA, TNF-α levels, and decreased SOD, GSH-PX enzyme activates and GSH levels of the tissues. ACA administration ameliorated OKA-induced memory impairment in rats. The ACA treatment also increased SOD and GSH-PX enzyme activation and GSH levels, and conversely decreased the levels of MDA, TNF-α. It was found that the numbers of the degenerated neurons and Caspase-3 positive cells of cortex and hippocampus regions were significantly reduced. ACA administration attenuates the oxidative stress and neuroinflammation of OKA-induced neurodegeneration; and ameliorates the cognitive decline and neurodegeneration.