title: ACA, an inhibitor phospholipases A2 and transient receptor potential melastatin-2 channels, attenuates okadaic acid induced neurodegeneration in rats.
abstract: OBJECTIVE
  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 PLA2inhibitor N-(p-amylcinnamoyl) Anthranilic Acid (ACA) in a neurodegenerative model induced by Okadaic Acid (OKA).
  
  
  METHODS
  OKA (200ng/10μl) was administered bilateral intracerebroventricularly as a single injection.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  ACA administration attenuates the oxidative stress and neuroinflammation of OKA-induced neurodegeneration; and ameliorates the cognitive decline and neurodegeneration.
authors.affiliation: Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey. Electronic address: murat.cakir@bozok.edu.tr.
authors.forename: Murat
authors.initials: M
authors.lastname: Cakir
authors.affiliation: Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey.
authors.forename: Halil
authors.initials: H
authors.lastname: Duzova
authors.affiliation: Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey.
authors.forename: Suat
authors.initials: S
authors.lastname: Tekin
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Bezmialem University, İstanbul, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Taslıdere
authors.affiliation: Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey.
authors.forename: Gul Busra
authors.initials: GB
authors.lastname: Kaya
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Inonu University, Malatya, Turkey.
authors.forename: Yılmaz
authors.initials: Y
authors.lastname: Cigremis
authors.affiliation: Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey.
authors.forename: Tuba
authors.initials: T
authors.lastname: Ozgocer
authors.affiliation: Department of Biostatistics, Faculty of Medicine, Inonu University, Malatya, Turkey.
authors.forename: Saim
authors.initials: S
authors.lastname: Yologlu
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D019319:Okadaic Acid / Q000633:toxicity*; D064801:Phospholipase A2 Inhibitors / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050053:TRPM Cation Channels / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D064801:Phospholipase A2 Inhibitors; D050053:TRPM Cation Channels; D062367:ortho-Aminobenzoates; D019319:Okadaic Acid; D054467:Phospholipases A2; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Alzheimer's disease; N-(p-amylcinnamoyl) anthranilic acid (ACA); Neurodegeneration; Okadaic acid; Phospholipases A(2); TRPM2 channel