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Folic acid improved memory and learning function in a rat model of neuroinflammation induced by lipopolysaccharide

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Abstract

Folic acid (FA) plays an important role in the maintenance of normal neurological functions such as memory and learning function. Neuroinflammation contributes to the progression of cognitive disorders and Alzheimer’s disease. Thus, this study aimed to investigate the effect of FA supplementation on cognitive impairment, oxidative stress, and neuro-inflammation in lipopolysaccharide (LPS)-injured rats. For this purpose, the rats were given FA (5–20 mg/kg/day, oral) for 3 weeks. In the third week, LPS (1 mg/kg/day; intraperitoneal injection) was given before the Morris water maze (MWM) and passive avoidance (PA) tests. Finally, the brains were removed for biochemical assessments. In the MWM test, LPS increased the escape latency and traveled distance to find the platform compared to the control group, whereas all doses of FA decreased them compared to the LPS group. The findings of the probe trial showed that FA increased the traveling time and distance in the target area. LPS impaired the performance of the rats in the PA test. FA increased delay and light time while decreasing the frequency of entry and time in the dark region of PA. LPS increased hippocampal levels of interleukin (IL)-6 and IL-1β. The hippocampal level of malondialdehyde was also increased but thiol content and superoxide dismutase activity were decreased in the LPS group. However, treatment with FA restored the oxidative stress markers along with a reduction in the levels of pro-inflammatory cytokines. In conclusion, FA could ameliorate the memory and learning deficits induced by LPS via normalizing the inflammatory response and oxidative stress markers in the brain.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This project originated from a master's thesis and the authors appreciate the Vice Chancellor for Research and Technology, Damghan University, Damghan, and Mashhad University of Medical Sciences for financial support.

Funding

Vice Chancellor for Research and Technology, Damghan University, Damghan, and Mashhad University of Medical Sciences, 4012086, Arezoo Rajabian.

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Authors and Affiliations

  1. Department of Animal Biology, School of Biology, Damghan University, Damghan, Iran

    Zahra Kioumarsi Darbandi & Iran Goudarzi

  2. Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Zahra Kioumarsi Darbandi, Sabiheh Amirahmadi & Mahmoud Hosseini

  3. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahmoud Hosseini

  4. Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran

    Arezoo Rajabian

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  1. Zahra Kioumarsi Darbandi
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Correspondence to Iran Goudarzi or Arezoo Rajabian.

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Ethical approval

All experimental procedures pursued the relevant guidelines and regulations of the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23, revised 1978) and were approved by the Ethics Committee of Mashhad University of Medical Sciences, Iran (4012086).

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Darbandi, Z.K., Amirahmadi, S., Goudarzi, I. et al. Folic acid improved memory and learning function in a rat model of neuroinflammation induced by lipopolysaccharide. Inflammopharmacol 32, 1401–1411 (2024). https://doi.org/10.1007/s10787-023-01314-w

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