The Neuroprotective Effect of α-Lipoic Acid and/or Metformin against the Behavioral and Neurochemical Changes Induced by Hypothyroidism in Rat

Abstract

<b><i>Objective:</i></b> The present study evaluates the neuroprotective effect of α-lipoic acid (ALA) and/or metformin (MET) on the behavioral and neurochemical changes induced by hypothyroidism. <b><i>Methods:</i></b> Rats were divided into control, rat model of hypothyroidism induced by propylthiouracil, and rat model of hypothyroidism treated with ALA, MET, or their combination. <b><i>Results:</i></b> Behaviorally, hypothyroid rats revealed impaired memory and reduced motor activity as indicated from the novel object recognition test and open-field test, respectively. Hypothyroidism induced a significant increase in lipid peroxidation (malondialdehyde [MDA]) and a significant decrease in reduced glutathione (GSH) and nitric oxide (NO) in the cortex and hippocampus. These were associated with a significant increase in tumor necrosis factor-α (TNF-α) and a significant decrease in brain-derived neurotrophic factor (BDNF). Hypothyroidism decreased significantly the levels of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) and reduced the activities of acetylcholinesterase (AchE) and Na⁺, K⁺-ATPase in the cortex and hippocampus. Treatment of hypothyroid rats with ALA and/or MET showed an improvement in memory function and motor activity. Moreover, ALA and/or MET prevented the increase in MDA and TNF-α, and the decline in GSH, NO, BDNF, 5-HT, NE, and DA. It also restored AchE and Na⁺, K⁺-ATPase activities in the studied brain regions. <b><i>Conclusion:</i></b> ALA and/or MET has a potential neuroprotective effect against the adverse behavioral and neurochemical changes induced by hypothyroidism in rats.