Khadrawy_2022_Neuroendocrinology__

OBJECTIVE: The present study evaluates the neuroprotective effect of alpha 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 (PTU), 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 (NORT) and open field test (OFT), respectively. Hypothyroidism induced a significant increase in lipid peroxidation (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-alpha (TNF-alpha) 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-alpha, 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.