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Folic acid attenuated learning and memory impairment via inhibition of oxidative damage and acetylcholinesterase activity in hypothyroid rats

Abstract

Hypothyroidism has been reported to be associated with cognitive decline. Considering the role of folic acid (FA) in cognitive performance, the present study was designed to investigate the effects of FA on hypothyroidism-induced cognitive impairment, oxidative damage, and alterations in acetylcholinesterase (AChE) activity in rat model of propylthiouracil (PTU)-induced hypothyroidism. In this study, PTU (0.05% in drinking water) and FA (5, 10, and 15 mg/kg, oral gavage) were administered for the rats during 7 weeks. Then, behavioral performance was tested using Morris water maze (MWM) and passive avoidance (PA) tasks. Finally, oxidative stress indicators and AChE activity were assayed in the brain tissues. The impairing effect of hypothyroidism on cognitive performance was markedly alleviated by FA especially at higher doses. In the MWM test, FA reduced escape latency and travelled distance, compared to the non-treated hypothyroid group. In the PA test, latency to enter dark chamber was significantly enhanced by FA compared to the non-treated hypothyroid group (p < 0.05–p < 0.001). Besides, FA attenuated AChE activity and malondialdehyde level but it increased activity of superoxide dismutase enzyme and total thiol content (p < 0.05–p < 0.001). In conclusion, our findings revealed that FA could improve learning and memory ability in hypothyroid rats. The observed protective effects may have been mediated through regulation of oxidative stress and AChE activity.

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Acknowledgements

The authors appreciate the Vice Chancellor for Research and Technology, Mashhad University of Medical Sciences for financial support (NO: 991073).

Funding

This study was funded by Vice Chancellor for Research and Technology, Mashhad University of Medical Sciences with the following grant number: 991073.

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Authors

Contributions

Mahmoud Hosseini conducted conception and design of the project, Sabiheh Amirahmadi, Somaieh Ahmadabady, Mahsa Akbarain, Kataneh Abrari, Arezoo Rajbian, and Farzaneh Vafaee performed the experiments. Mahmoud Hosseini, Arezoo Rajbian, and Farzaneh Vafaee prepared a draft of the manuscript. Mahmoud Hosseini, Arezoo Rajbian, Farzaneh Vafaee performed statistical analysis. Mahmoud Hosseini, Farzaneh Vafaee, and Arezoo Rajbian provided final revision of the manuscript. All authors contributed to manuscript preparation and approved the submitted version.

Corresponding authors

Correspondence to Farzaneh Vafaee or Arezoo Rajabian.

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The authors declare no conflict of interest.

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All procedures performed in this studies including animals were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by Ethical Committee of the Animal Research of Mashhad University of Medical Sciences (Ethical code: IR.MUMS.MEDICAL.REC.1399.639).

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Amirahmadi, S., Hosseini, M., Ahmadabady, S. et al. Folic acid attenuated learning and memory impairment via inhibition of oxidative damage and acetylcholinesterase activity in hypothyroid rats. Metab Brain Dis (2021). https://doi.org/10.1007/s11011-021-00815-3

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Keywords

  • Cholinergic dysfunction
  • Folic acid
  • Hypothyroidism
  • Learning and memory deficit
  • Oxidative injury