Korean J Physiol Pharmacol.  2022 Nov;26(6):415-425. 10.4196/kjpp.2022.26.6.415.

Myricetin prevents sleep deprivation-induced cognitive impairment and neuroinflammation in rat brain via regulation of brain-derived neurotropic factor

• Sur B
• Lee B

• KMID: 2534518
• DOI: http://doi.org/10.4196/kjpp.2022.26.6.415

Abstract

Memory formation in the hippocampus is formed and maintained by circadian clock genes during sleep. Sleep deprivation (SD) can lead to memory impairment and neuroinflammation, and there remains no effective pharmacological treatment for these effects. Myricetin (MYR) is a common natural flavonoid that has various pharmacological activities. In this study, we investigated the effects of MYR on memory impairment, neuroinflammation, and neurotrophic factors in sleepdeprived rats. We analyzed SD-induced cognitive and spatial memory, as well as pro-inflammatory cytokine levels during SD. SD model rats were intraperitoneally injected with 10 and 20 mg/kg/day MYR for 14 days. MYR administration significantly ameliorated SD-induced cognitive and spatial memory deficits; it also attenuated the SD-induced inflammatory response associated with nuclear factor kappa B activation in the hippocampus. In addition, MYR enhanced the mRNA expression of brainderived neurotropic factor (BDNF) in the hippocampus. Our results showed that MYR improved memory impairment by means of anti-inflammatory activity and appropriate regulation of BDNF expression. Our findings suggest that MYR is a potential functional ingredient that protects cognitive function from SD.

Keyword

Brain-derived neurotrophic factor; Flavonoids; Inflammation; Memory; Sleep deprivation

Figure

• 

  Fig. 1 Experimental protocols for sleep deprivation (SD)-induced memory impairment behaviors and myricetin (MYR) treatment in rats. Rats were divided into groups (n = 6–7 rats/group), then subjected to the indicated experimental protocols. OFT, open-field test; 8-arm RAM task, eight-arm radial maze task.

• 

  Fig. 2 Results of body weight and food intake analyses of rats subjected to 14 days of sleep deprivation (SD). (A) Body weight and (B) food intake were significantly lower in SD-exposed rats than in saline (SAL)-treated rats (significant main effect of SD exposure vs. control handling). Data are shown as means ± SEM. *p < 0.05 vs. SAL group.

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  Fig. 3 Effects of myricetin (MYR) on the number of errors in the 8-arm RAM task in sleep deprivation (SD)-induced rats. The task was started during the second week after SD, and four trials were performed each day. (A) Comparison of rat performance during the acquisition phase and (B) short-term memory test. 8-arm RAM task, eight-arm radial maze task; WPF, wide platform; SAL, saline; ATI, alprazolam. *p < 0.05, **p < 0.01, ***p < 0.001 vs. SAL group; #p < 0.05, ##p < 0.01 vs. SD group.

• 

  Fig. 4 The Morris water maze test was used to assess the effects of myricetin (MYR) on spatial learning and memory. Time to escape (latency) from the water onto a submerged platform during acquisition trials, (A) a submerged platform during acquisition trials, (B) swimming speed, (C) percentage of time spent in the target quadrant, (D) percentage of distance traversed in the target quadrant, (E) path efficiency to reach the target zone, and (F) number of entries to the target zone outcome measures. SD, sleep deprivation; SAL, saline; WPF, wide platform; ATI, alprazolam. **p < 0.01 vs. SAL group; #p < 0.05, ##p < 0.01 vs. SD group.

• 

  Fig. 5 Effects of MYR administration on locomotor activity in the OFT during SD. MYR, myricetin; OFT, open-field test; SAL, saline; WPF, wide platform; ATI, alprazolam.

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  Fig. 6 Effects of myricetin (MYR) on tumor necrosis factor (TNF)-α (A), interleukin (IL)-1β (B), IL-6 (C), IL-8 (D), IL-4 (E), and IL-12 (F) concentrations in the hippocampus of rats exposed to sleep deprivation (SD), determined by ELISA analysis. SAL, saline. *p < 0.05, **p < 0.01, ***p < 0.001 vs. SAL group; #p < 0.05, ##p < 0.01 vs. SD group.

• 

  Fig. 7 Effects of myricetin (MYR) on the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) mRNA in rats with sleep deprivation (SD)-induced hippocampal impairment. (A) PCR bands on agarose gels and relative intensities are shown. Expression levels of BDNF and TrkB mRNAs were normalized to glyceraldehyde 3-phosphate dehydrogenase mRNA as the internal control, (B) activation of nuclear factor kappa B (NF-κB) in the hippocampus after MYR treatment. Western blot analysis of protein expression levels of NF-κB. SAL, saline; WPF, wide platform; ATI, alprazolam. *p < 0.05, ***p < 0.001 vs. SAL group; #p < 0.05, ##p < 0.01 vs. SD group.

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