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

作者：Cakir Murat^*; Duzova Halil; Tekin Suat; Taslidere Elif; Kaya Gul Busra; Cigremis Yilmaz; Ozgocer Tuba; Yologlu Saim

来源：Life Sciences, 2017, 176: 10-20.

DOI：10.1016/j.lfs.2017.03.022

• Okadaic acid
• N-(p-amylcinnamoyl) anthranilic acid (ACA)
• Neurodegeneration
• TRPM2 channel
• Phospholipases A(2)
• Alzheimer's disease

Aim: 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).
Main methods: OKA (200 ng/10 mu l) 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, beta-amyloid positive cells in the hippocampus and cerebral cortex. Furthermore, OKA-treated rats exhibited significantly increased MDA, TNF-alpha 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-alpha. 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.

• 出版日期2017-5-1