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

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Abstract

Aim:

In recent studies, it has been shown that the Transient Receptor Potential Melastatin-2 Channels (TRPM2) and Phospholipases A2 (PLA2) inhibitors may have a protective effect on neurons. This study was aimed to investigate the protective effect of TRPM2 and PLA2 inhibitor N-(p-amylcinnamoyl) Anthranilic Acid (ACA) in a neurodegenerative model induced by Okadaic Acid (OKA).

Main methods:

OKA (200 ng/10 μl) was administered bilateral intracerebroventricularly as a single injection.

Key findings:

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.

Significance:

ACA administration attenuates the oxidative stress and neuroinflammation of OKA-induced neurodegeneration; and ameliorates the cognitive decline and neurodegeneration.

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