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

Objective: 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.
Methods: Rats were divided into control, rat model of hypothyroidism induced by propylthiouracil, and rat model of hypothyroidism treated with ALA, MET, or their combination.
Results: 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.
Conclusion: ALA and/or MET has a potential neuroprotective effect against the adverse behavioral and neurochemical changes induced by hypothyroidism in rats.
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