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

Sabiheh Amirahmadi,Kataneh Abrari,Mahsan Akbarian,Farzaneh Vafaee,Somaieh Ahmadabady,Mahmoud Hosseini,Arezoo Rajabian

doi:10.1007/s11011-021-00815-3

Sabiheh Amirahmadi, Kataneh Abrari + Show 5 more

Open Access

https://doi.org/10.1007/s11011-021-00815-3

Copy DOI

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 15mg/kg, oral gavage) were administered for the rats during 7weeks. 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.

Highlights

Thyroid hormones (THs) including thyroxine (T4) and triiodothyronine (T3) are of great importance for neuronal developmental stages and play a key role in neurons maturation, migration, differentiation, and signaling
Given that hypothyroidism is one of the most common diseases that leads to cognitive impairment and since folate deficiency is one of the most important dietary health problems worldwide, this study evaluated the effect of folic acid (FA) on learning and memory, oxidative stress indicators and acetylcholine esterase (AChE) activity in hypothyroid rats
The time latency and the distance traveled to reach the platform during the 5-day training in the Morris water maze (MWM) test in hypothyroid group were significantly increased compared to the control group (P

Summary

Introduction

Thyroid hormones (THs) including thyroxine (T4) and triiodothyronine (T3) are of great importance for neuronal developmental stages and play a key role in neurons maturation, migration, differentiation, and signaling. THs-related disorders during development and adulthood can lead to serious clinical problems including cognitive dysfunction (Bernal 2007). Since concentrations of THs decrease with increasing age, hypothyroidism is common among elderlies and can lead to symptoms of severe cognitive impairment, including deterioration of learning and memory, perception, reasoning, problem solving, decision making and language by affecting energy consumption processes such as glucose metabolism, which is necessary for neurotransmission (Bégin et al 2008; Annerbo and Lökk 2013). Clinical and experimental reports suggest that THs replacement therapy can partially reverse negative effects of hypothyroidism on learning and memory, but a full recovery of T3 content in target tissues, especially in the brain, is far from reach and more appropriate treatments are required (Chaalal et al 2019). Some of the vitamins have been shown to have beneficial effects on hypothyroidism-related cognitive dysfunctions (Beheshti et al 2017; Baghcheghi et al 2018a; Baghcheghi et al 2020)

Methods

Results

Conclusion