title: Riluzole ameliorates learning and memory deficits in Aβ25-35-induced rat model of Alzheimer's disease and is independent of cholinoceptor activation.
abstract: Alzheimer's disease (AD) is a major global public health concern and social care problem that is associated with learning, memory, and cognitive deficits. Riluzole is a glutamate modulator which has shown to improve memory performance in aged rats and may be of benefit in Alzheimer's disease. In the present study, its beneficial effect on attenuation of learning and memory deficits in Aβ25-35-induced rat model of AD was assessed. Riluzole administration at a dose of 10mg/kg/day p.o. improved spatial memory in Morris water maze and retention and recall in passive avoidance task and its protective effect was not neutralized following intracerebroventricular microinjection of muscarinic or nicotinic receptor antagonists. Further biochemical analysis showed that riluzole pretreatment of intrahippocampal Aβ-microinjected rats is able to attenuate hippocampal AChE activity and lower some oxidative stress markers, i.e. MDA and nitrite, with no significant change of the defensive enzyme catalase. Furthermore, riluzole prevented hippocampal CA1 neuronal loss and reduced 3-nitrotyrosine immunoreactivity. It is concluded that riluzole could exert a protective effect against memory decline induced by intrahippocampal Aβ25-35through anti-oxidative, anti-cholinesterase, and neuroprotective potential and its beneficial effect is possibly independent of cholinoceptor activation.
authors.affiliation: Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Mokhtari
authors.affiliation: Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: tmojarad@yahoo.com.
authors.forename: Tourandokht
authors.initials: T
authors.lastname: Baluchnejadmojarad
authors.affiliation: Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Nikbakht
authors.affiliation: Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Monireh
authors.initials: M
authors.lastname: Mansouri
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran. Electronic address: mehjour@yahoo.com.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Roghani
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D010446:Peptide Fragments / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism*; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016229:Amyloid beta-Peptides; D018691:Excitatory Amino Acid Antagonists; D010446:Peptide Fragments; D011950:Receptors, Cholinergic; C074636:amyloid beta-protein (25-35); D019782:Riluzole
keywords: Acetylcholinesterase; Alzheimer’s disease; Aβ(25–35); Cholinergic receptor; Learning and memory; Oxidative stress; Riluzole