Effects of Levothyroxine on Behavior and Cognitive Decline in a Rat Model of Multiple Sclerosis: A Biochemical Study

Abstract

Background: Multiple sclerosis (MS) is an autoimmune disease in the central nervous system (CNS) that affects the development and physiological function of the brain and causes memory impairment. Objectives: Due to the anti-inflammatory and antioxidant role of levothyroxine (L-T4) on myelin production and adult cerebral function, this study aimed to evaluate the effects of L-T4 on the improvement of cognitive deficits and cerebral inflammation. Methods: Forty Wistar rats were randomly divided into five groups: (1) sham, (2) L-T4, (3) MS, (4) MS receiving L-T4, and (5) Betaferon. For MS induction, lysolecithin was injected into the CA1 of the hippocampus. Rats received L-T4 intraperitoneally at a dose of 100 μg/kg in the second and fourth groups. The shuttle box and Morris water maze tests were used to investigate passive avoidance and spatial memory, respectively. Also, the hippocampal concentrations of total antioxidant capacity (TAC), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and c-reactive protein (CRP) were measured to investigate molecular changes. Results: Path length (P < 0.001, P = 0.0015, and P = 0.002 on days 1 to 3, respectively) and latency time (P < 0.001 on the second and third days) increased, but the speed of movements (P < 0.001) and time spent in goal quarter decreased in MS-induced groups (P < 0.001). Treatment with L-T4 for 14 days significantly reversed path length and speed (P < 0.001 and P = 0.0315 on the second and third days), latency time (P < 0.01), speed (P < 0.001 and P = 0.0038 on the second and third days), and time spent in goal quarter (P = 0.1203) in the MS group. The hippocampal concentrations of MDA (P = 0.0010), TNF-α (P = 0.0251), and CRP (P = 0.0065) were significantly lower in the MS group treated with L-T4 than in the MS group. Also, the hippocampal concentration of TAC was significantly increased (P = 0.0375) in the MS group receiving L-T4. Conclusions: It seems that treatment with L-T4 can prevent cognitive impairment caused by MS induction. Ameliorative effects of L-T4 may be due to the reduction of inflammation and oxidative stress. Therefore, L-T4 can be used as an effective agent in the treatment of MS.