Peripheral and central administration of T3 improved the histological changes, memory and the dentate gyrus electrophysiological activity in an animal model of Alzheimer's disease.

Abstract

The amyloid beta (Aβ) induced Alzheimer's disease (AD) is associated with formation the amyloid plaques, cognitive impairments and decline in spontaneous discharge of neurons. In the current study, we evaluated the effect of subcutaneous (S. C) and intrahippocampal (I. H) administrations of triiodothyronine (T3) on the histological changes, memory and the dentate gyrus (DG) electrophysiological activity in an animal model of AD. Eighty adult male Wistar rats (250-300g) were divided randomly into five groups: Sham-Operated (Sh-O), AD+Vehicle (S. C), AD+Vehicle (I. H), AD+ T3 (S. C) and AD+T3 (I. H). In order to induce animal model of AD, Aβ (10ng/μl, bilaterally) were injected intrahippocampally. Rats were treated with T3 and/or normal saline for 10days. Passive avoidance and spatial memory were evaluated in shuttle box apparatus and Morris water maze, respectively. Neuronal single unit recording was assessed from hippocampal DG. The percent of total time that animals spent in target quarter, the mean latency time (sec), the step through latency and the average number of spikes/bin were decreased significantly in AD rats compared with the Sh-O group (p<0.001) and were increased significantly in AD groups that have received T3 (S. C and I. H) in compared with AD group (p<0.01, p<0.001). Also, formation of amyloid plaques was decreased in AD rats treated with T3.The results showed that T3 injection (S. C and I. H), by reduction of neural damage and increment of neuronal spontaneous activity improved the memory deficits in Aβ-induced AD rats.