title: Central and peripheral administrations of levothyroxine improved memory performance and amplified brain electrical activity in the rat model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is associated with cognitive impairments and a decline in the spontaneous neuronal discharge. In the current study, we evaluated the effect of subcutaneous (S.C.) and intrahippocampal (I.H.) administrations of levothyroxine (LT-4) on the passive avoidance and spatial memory, as well as electrophysiological activity in an animal model of AD. One hundred-sixty male Wistar rats were divided into two main groups. The S.C. group included two Sham and four AD (vehicle or L-T4 25, 50 & 100μg/kg); and the I.H. had consisted of two Sham and two AD (vehicle or L-T4 10μg/kg) subgroups. To make an animal model of AD, amyloid beta (Aβ) plus ibotenic acid (Ibo) were injected I.H. Rats were treated with L-T4 and/or normal saline for ten days. Passive avoidance and spatial memory were evaluated in shuttle box and Morris water maze, respectively. Neuronal single unit recording was assessed from hippocampal dentate gyrus (DG). Results showed that the mean latency time (s) increased significantly (p<0.001) in AD animals and decreased significantly in both S.C. and I.H. L-T4 injected AD animals, compared with the AD group (p<0.001). The percentage of total time that animals spent in goal quarter and the step through latency decreased significantly in AD rats (p<0.001) and increased significantly in both S.C. and I.H. L-T4 injected AD animals in comparison with the AD group (p<0.01, p<0.001). Data showed that the average number of spikes/bin significantly decreased in the AD group (p<0.001). The S.C. and I.H. L-T4 injections in AD rats significantly increased the spike rate in comparison to the AD group (p<0.001). In conclusion, both S.C. and I.H. injections of L-T4 alleviated memory deficits and spontaneous neuronal activity in Aβ-induced AD rats. Also, I.H. microinjection of L-T4 had more beneficial effects on memory and neuronal electrophysiological activity in comparison to S.C. administration.
authors.affiliation: Physiology Research Center, Department of Physiology, Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Sahreh
authors.initials: S
authors.lastname: Shabani
authors.affiliation: Physiology Research Center, Department of Physiology, Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Sarkaki
authors.affiliation: Physiology Research Center, Department of Physiology, Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Seyyed
authors.initials: S
authors.lastname: Ali Mard
authors.affiliation: Physiology Research Center, Department of Physiology, Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Akram
authors.initials: A
authors.lastname: Ahangarpour
authors.affiliation: Cellular and Molecular Research Center, Department of Anatomical Sciences, Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Layasadat
authors.initials: L
authors.lastname: Khorsandi
authors.affiliation: Physiology Research Center, Department of Physiology, Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: farbood_y@yahoo.com.
authors.forename: Yaghoob
authors.initials: Y
authors.lastname: Farbood
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D065852:Spatial Memory / Q000187:drug effects*; D013974:Thyroxine / Q000008:administration & dosage*
chemical_list: D013974:Thyroxine
keywords: Alzheimer's disease; Levothyroxine; Memory; Rat; Single-unit recording