Role of proNGF-p75NTRin isoflurane-induced cognitive impairment in aging mice / 中国病理生理杂志

ABSTRACT

AIM:To investigate the role of specific binding of precursor form of nerve growth factor(proNGF) to p75NTR(proNGF-p75NTR)in isoflurane-induced cognitive impairment in aging mice.METHODS: Aging C57BL/6J male mice were randomly divided into 3 groupscontrol group,isoflurane(Iso)group and p75NTR specific inhibitor 2-ami-no-3-methyl-pentanoic acid amide(LM11A-31,LM)+isoflurane(LM+Iso)group.Aging C57BL/6J mice in Iso group and LM+Iso group were exposed to isoflurane,and the mice in control group were exposed to air.The mice in LM+Iso group were treated with LM,which dissolved in normal saline water and was administered daily by oral gavage at 50 mg· kg-1· d-1for 1 month.The mice in control group and Iso group received an equivalent volume of normal saline by the same route.Arterial blood gas analysis was conducted to detect the physiological state of the mice after isoflurane exposure. Morris water maze was performed to evaluate the cognitive function.The protein levels of proNGF,p75NTR,phosphorylated p38 MAPK and cleaved caspase-3 were determined by Western blot.RESULTS: Compared with the control group, the protein expression of proNGF and p75NTR in the hippocampus of Iso group was significantly elevated(P<0.05).The phos-phorylation level of p38 MAPK was higher in Iso group than that in control group(P<0.05),which was reduced in LM +Iso group significantly(P<0.05).A significant increase in the protein level of cleaved caspase-3 was observed in Iso group as compared with control group(P<0.05), while LM11A-31 treatment reversed this elevation significantly(P<0.05).The escape latency prolonged and the number of crossing the original platform location reduced in Iso group com -pared with control group(P<0.05), which were reversed by LM11A-31 in LM+Iso group(P<0.05).CONCLU-SIONProNGF-p75NTR probably plays an vital role in the apoptotic pathway activation and the cognitive dysfunction in ag -ing mice exposure to isoflurane,which provides a potential target for clinical intervention.