Abstract��OBJECTIVE To investigate the effect of ��-secretase inhibitor DAPT in inflammation-induced brain white matter injury in neonatal mice.METHODS Sixty C57BL/10J neonatal mice are randomly divided into control group, control+DAPT (10 mg��kg-1) group, inflammation (LPS) group, LPS+DAPT group (inflammation exposure after 10 mg��kg-1 DAPT treatment). All neonatal mice were killed and brain was removed to the following observation and detection:at P5, the mRNA expression variation of IL-1��, IL-8,TNF-��,Hes1 and NICD by Real-time PCR methods. Oligodendrocytes were identified by immunofluorescence staining. Myelin basic protein (MBP) protein expression was detected by Western blot assay.RESULTS LPS group showed brain injury characterized by inhibition of brain development. There were significant differences in mRNA expression of IL-1��, IL-8, TNF-��, Hes1 and NICD between LPS+DAPT group and LPS group (P<0.05), and the mRNA expression of IL-1��, IL-8,TNF-��,Hes1 and NICD in inflammation-treated were significantly increased than control group (P<0.05). The results showed more expression of MBP in LPS+DAPT group compared with LPS group (P<0.05). Compared with the blank control group, which was obviously decreased after 48 h of inflammation (P<0.05).CONCLUSION Inflammation leads to abnormal of notch signal expression in neonatal mice, and which is shows inflammation involved in brain damage.Its mechanism is probably associated with the maturation of oligodendrocytes.
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LIU Guang-jian, JI Liu, WANG Da-guo, LUO Xiang-hong. Effects of ��-Secretase Inhibitor DAPT on Inflammation-Induced White Matter Damage in Neonatal Mice. Chinese Pharmaceutical Journal, 2018, 53(13): 1083-1087.
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