| Objectives: To investigate the dynamic changes of brain-derived neurotrophic factor(brain derived neurotrophic factor,BDNF)and interleukin-4(Interleukin-4,IL-4)in the mice hippocampus during different periods of acute sleep deprivation,and to further explore whether there is a correlation between them.And a preliminary study was conducted on the possible mechanism of action between the IL-4 and BDNF,which provided a possible theoretical basis for the effects of sleep deprivation on hippocampal learning and memory functions.Methods: 1.C57BL/6J male mice were randomly divided into normal control group(Cage control,CC),REM sleep deprivation 1d group(REM sleep deprivation 1 day,SD1d),REM sleep deprivation 2d group(SD2d),REM sleep deprivation 3d group(SD3d)and AS1517499 treatment before the REM sleep deprivation 1d group(AS1517499 + SD1d),12 mice in each group.After 1 week of cage feeding,CC group was killed at 9:00AM.SD1 d group was killed after sleep deprivation 1 day at 9:00 AM,SD2 d group was killed after 2 days of sleep deprivation at the same time,and SD3 d group was killed after 3 days of sleep deprivation at the same time.AS1517499+SD1d group was injected intraperitoneally with AS1517499 for 7 consecutive days,and then killed after 1 day of sleep deprivation at 9:00 AM.2.RT-PCR method was used to observe the expression of BDNF,IL-4 and STAT6 mRNA in the hippocampus of mice in each group.The protein expression of BDNF,IL-4 and STAT6 in the hippocampus of each group were observed by ELISA.Results: 1.RT-PCR showed that the relative expression levels of BDNF,IL-4 and STAT6 mRNA in the hippocampus of the SD1 d group were higher than those in the CC group(P = 0.045,P = 0.19,P =0.041,respectively);There was no significant difference in the relative expression of BDNF?IL-4 and STAT6 mRNA in SD2 d group and CC group(P = 0.297,P=0.837,P >0.5,respectively).The relative expression of BDNF,IL-4 and STAT6 mRNA in the SD3 d group was significantly lower than that in the CC group(P <0.001,P= 0.008,P<0.001,respectively).2.ELISA demonstrated that the expression of BDNF,IL-4 and STAT6 in the hippocampus of SD1 d group was higher than those in CC group.The difference was statistically significant(P = 0.029,P<0.001,P=0.017,respectively);Compared with the CC group,BDNF,IL-4 and STAT6 in SD2 d group were no significant difference(P > 0.5,P=0.13,P=0.073,respectively);SD3d group had significantly lower expression of BDNF,IL-4 and STAT6 than the CC group(P<0.001).3.Pearson correlation analysis showed that there was a positive correlation between the changes of IL-4 and BDNF protein expression in hippocampus during sleep deprivation,P<0.001,correlation coefficient r=0.863.4.RT-PCR showed that the relative expression of BDNF,IL-4 and STAT6 mRNA in the hippocampus of the AS1517499+SD1d group was significantly lower than those in the SD1 d group.The difference was statistically significant(P<0.001).The ELISA showed that the protein expression of BDNF,IL-4 and STAT6 in AS1517499+SD1d group were significantly lower than those in SD1 d group,and the difference was statistically significant(P<0.001).Conclusions: 1.Short-term(24h)sleep deprivation may increase BDNF,IL-4 levels in the hippocampus of mice,suggesting that short-term sleep deprivation is a stimulus to the body and may activate neuroprotective factors BDNF and anti-inflammatory cytokines IL-4 Increased expression,both of which may be a self-protection response of the body after sleep deprivation.2.With the prolonged sleep deprivation,the expression levels of BDNF and IL-4 in the hippocampus of mice decreased to baseline levels at 48 hours after sleep deprivation,and the expression of BDNF and IL-4 in the hippocampus of mice after prolonged sleep deprivation time to 72 hours decreased below the baseline level.These changes reflected that the defense mechanism of the body against adverse stimuli may be reduced with the extension of sleep deprivation time,which may be one of the possible mechanisms of sleep deprivation causing nerve damage.3.There is a strong positive correlation between the expression of IL-4 and BDNF in the mouse hippocampus during sleep deprivation.4.During sleep deprivation,the expression of transcription factor STAT6 that specifically binds to IL-4 is consistent with the expression of IL-4 and BDNF.After inhibition of STAT6,the expression of BDNF decreased after 24 hours of sleep deprivation,suggesting that during sleep deprivation IL-4 may promote the production of BDNF through the JAK/STAT6 pathway,which may be one of the protective mechanisms of IL-4 on brain nerve cells. |
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