Relationship Between Sleep Deprivation And The Expression Of BDNF,NGF And Its Receptor In Mouse Hippocampus And Its Effect On Amyloid Protein Synthesis

Objectives: Study the m RNA transcription level and protein expression levels of brain deri ved neurotrophic factor(BDNF)、nerve growth factor(NGF)and there receptor tyrosine kinase B(Trk B),tyrosine kinase A(Trk A),nerve nutriment receptor(p75 neurotrophin receptor),beta-secretase(BACE)in the hippocampus of mic e that experienced REM sleep deprivation for 3 consecutive days and discontin uous REM sleep deprivation for 7 days.As well as studying the possible ass ociation of p75 receptor changes with BACE function.To investigate the possi ble mechanism of the effects of sleep deprivation on the cognitive function in the matter of changes of neurotrophins and their receptors in mouse hippocamp us after sleep deprivation.Method: 1.The model of REM sleep deprivation was established using modified multipl e platform method(MMPM).Select 6 weeks old male C57BL/6J mice after ra ised in cage for 3-4 days they were randomly divided into normal control gro up(cage control,CC),REM sleep deprivation group for 3 days(SD3d)and R EM sleep deprivation group for 7 days(SD7d).There are 12 mice in each gr oup.The mice of each group were fed 3-4 days in the cage,the mice of CC group were put to death at 9 am.The SD3 d group started sleep deprivation,3 days later,these mice were put to death at 9 am.The SD7 d group mi ce were deprived sleep for 7 days,but these mice were put in the normal rat cage for rest at 18:00-21:00 without sleep deprivation everday,and was put to death at 9 am after 7 days of sleep deprivation.2.Using Rt-PCR method to observe the changes of gene levels in the mice hi ppocampus of BDNF,NGF and its receptor Trk B,Trk A,p75,and BACE.3.Western Blot method was used to detect the protein expression levels in the mice hippocampus of BDNF,NGF and its receptor Trk B,Trk A,p75,and BA CE.Results: 1.The expression of BDNF and Trk B in the hippocampal area of the mice aft er REM sleep deprivation for 3 days was reduced compared with the CC grou p,and the difference was significant(P < 0.05).The expression of BDNF an d Trk B after REM sleep deprivation for 7 days was increased compared to the control group and the SD3 d group,and the difference was significant(P < 0.005).2.In the mice hippocampus after REM sleep deprivation for 3 days,The expr ession NGF and Trk A made no change than normal control group,no significa nt change was showen(P > 0.05),REM sleep deprivation after 7 days the ex pression of NGF and Trk A increased compared to CC group and SD3 d group,and the difference was statistically significant(P < 0.05).3.Sleep deprivation after 3 days in the hippocampus of mice,the expression of p75 compared to CC group have no significant change(P > 0.05),REM sl eep deprivation after 7 days,the expression of p75 compared to the CC group and SD3 d group were increased,and the difference of data was statistically s ignificant(P < 0.05)4.REM sleep deprivation after 3 days,in the mice hippocampus,the expression of BACE expressed no significant change(P > 0.05),After REM sleep de privation for 7 days,The expression of BACE compared to CC group and SD3d group was increased,and the difference was statistically significant(P < 0.05).Conclusions: 1.The m RNA and protein expression of BDNF and high-affinity receptor Trk B in the hippocampus of mice after deprivation of REM sleep for 3d and 7d showed a trend of decreasing first and then increasing.The decreased expression of BDNF and Tr KB in the DS3d mice may be one of the mechanisms of impairment of central nervous system function after REM sleep deprivation.T he increase in expression after 7 days of REM sleep deprivation may be related to the activation of neuroprotective mechanisms.2.After 3 days and 7 days of REM sleep deprivation,the m RNA and protein levels of NGF and Trk A in the hippocampus of the mice showed the tendency to stay the same first and then increase.After 3 days of continuous REM sleep deprivation,the expression of NGF and Trk A in the mouse hippocampush as not changed significantly,which may be related to a slight delay in the cha nges of NGF after REM sleep deprivation.After 7 days of REM sleep deprivation,the expression of NGF and Trk A in the hippocampus of mice increased,indicating that NGF may be one of the factors involved in the neuroprotectiv e mechanism after sleep deprivation.3.After 3 and 7 days of REM sleep deprivation,the m RNA and protein expression of p75 neurotrophin receptor in the hippocampus of the mice showeda tendency of first stay the same and then increase.The expression of p75 in REM sleep deprivation at 3d had no significant changes but increased after 7d REM sleep deprivation.No significant changes in p75 expression in the hippoc ampus of mice after 3 days of REM sleep deprivation may be associated with short sleep deprivation time and corresponding neuromodulation genes was not activated.The increased expression of p75 in the hippocampus of the 7-days REM sleep deprivation group suggests that sleep deprivation injury may prom ote the deposition of hippocampal Aβ by activating this receptor.4.After 3 and 7 days of REM sleep deprivation,the expression of Aβ-generated rate-limiting enzyme BACE in the hippocampus of mice stay the same first and then increased.The increase of this expression may be related to the inc rease of p75 expression.The expression changes of BACE may be related to cognitive function loss caused by sleep deprivation.