title: Non-selective NSAIDs improve the amyloid-β-mediated suppression of memory and synaptic plasticity.
abstract: Alzheimer's disease (AD) is characterized by the formation of amyloid beta (Aβ) plaques in the brain. Dysfunctional excitatory synaptic transmission and neuronal plasticity are generally accepted as primary events in the development of AD. There is evidence to suggest that both COX-1 expression and COX-2 expression are changed in the brain of AD patients. However, the impact of COX-dependent mechanisms on synaptic dysfunction underlying the memory deficit is not fully elucidated. In the present study effects of non-selective NSAIDs (aspirin and sodium salicylate) on associated memory impairment as well as Aβ-mediated suppression of synaptic plasticity in the hippocampus were examined. Aβ1-42 (5μg/μl) and ibotenic acid (5μg/μl) were injected bilaterally into the dorsal hippocampus of rats and the spatial memory and long term potentiation (LTP) were assessed by water maze performance and in vivo field potential recording, respectively. Field excitatory post synaptic potentials (fEPSP) were recorded from stratum radiatum of area CA1 following Schaffer collateral stimulation. Behavioral study revealed that both sub-chronic high dose of sodium salicylate (SS) and chronic low dose of aspirin improved the spatial memory impairment of Aβ treated rats, however the effects of SS were lower than those of aspirin. Animals treated with SS and aspirin showed a significant decrease in escape latency (SS: F(1, 24)=15.85, p<0.01, aspirin: F(1, 22)=25.24, p<0.001, ANOVA). Furthermore, in probe test, animals treated with aspirin (p<0.05) but not SS (p>0.05) spent more time (one-way ANOVA) in target quadrant zone. Both applied drugs restored the suppression of fEPSP slope LTP that was induced by Aβ treatment (unpaired t-test, p<0.001). Aspirin showed a preventative effect also against Aβ-induced changes in LTP and memory task when applied before Aβ administration. Since aspirin and SS improved synaptic dysfunction, we can suggest that COX-dependent mechanisms may play a role in synaptic dysfunction in an experimental model of AD.
authors.affiliation: Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Doost Mohammadpour
authors.affiliation: Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: nargeshosseinmardi@yahoo.comn.
authors.forename: Narges
authors.initials: N
authors.lastname: Hosseinmardi
authors.affiliation: Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mahyar
authors.initials: M
authors.lastname: Janahmadi
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Fathollahi
authors.affiliation: Neuroscience Research Center, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Motamedi
authors.affiliation: Department of Physiology and Pharmacology, Qom University of Medical Sciences and Health Services, Qom, Iran.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Rohampour
keywords: Alzheimer's disease; Aspirin; Learning and memory; Neuro-inflammation; Sodium salicylate; Synaptic plasticity