MLC901 during sleep deprivation rescues fear memory disruption in rats

Abstract

Several lines of evidence suggest that sleep deprivation disrupts cognitive and emotional abilities and changes the expression of distinctive categories of genes in the brain. In the present study, saline- or MLC901 (a traditional Chinese medicine)-treated male Wistar rats were first submitted to a modified water box (for 24-h sleep deprivation) and then trained in contextual and tone fear conditioning tasks with the purpose to evaluate the effect of MLC901 during sleep deprivation on fear memory retention. Hippocampal mRNA measurement was performed by reverse transcription-polymerase chain reaction (RT-PCR). We found that the exposure of rats to 24 h of sleep deprivation impaired contextual and tone fear memory retention, while administration of MLC901 (0.2, 0.4, and 0.8 mg/kg, once/12 h; i.p.) during sleep deprivation abolished memory deficits. Meanwhile, different doses of MLC901 alone had no effect on performance in both tasks. We observed that MLC901 increased the expression levels of pro-apoptotic BAD, anti-apoptotic Bcl-xL, and Tfam as an index of mitochondrial biogenesis compared to sleep-deprived rats, while MLC901 during sleep deprivation increased BAX, BAD, and Bcl-xL compared to the control group. Sleep deprivation decreased BAX and Tfam, by itself. MLC901 only decreased BAX and Tfam and increased BAD level compared to the non-sleep-deprived control group. It is suggested that MLC901 might be a therapeutic option for memory impairment during sleep deprivation.

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Authors

Contributions

AM acquired the animal data and wrote the manuscript. MN, ME, MH, and MZ were responsible for the study concept, design, and proteomics analysis as well as assisted with the data analysis and interpretation of findings. All authors critically reviewed the content and approved the final version for publication.

Corresponding authors

Correspondence to Mehrdad Hashemi or Mohammad-Reza Zarrindast.

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The study was carried out in accordance with ethical standards in all aspects.

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The authors declare that they have no conflict of interest.

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Nasehi, M., Mohammadi, A., Ebrahimi-Ghiri, M. et al. MLC901 during sleep deprivation rescues fear memory disruption in rats. Naunyn-Schmiedeberg's Arch Pharmacol 392, 813–821 (2019). https://doi.org/10.1007/s00210-018-01612-z

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Keywords

  • Sleep deprivation
  • MLC901
  • Fear memory conditioning
  • Rat