Effects Of Sulforaphane And Vitamin E On Spatial Learning And Memory Ability In Lead-exposed Mice And Study On Its Mechanism

ObjectTo investigate the effects of sulforaphane?SFN?and vitamin E?VitE?on spatial learning and memory ability,oxidative stress and proteins associated Alzheimer's lesions of hippocampus in mice whose mothers exposed to lead at lactation and pre-pregnancy.To provide a theoretical basis for drugs of the early lead exposure and AD-like lesions.MethodsA total of 33 KunMing mice at the age of 8 weeks?11 male,22 female?.After one week of adaptive feeding,mice were divided into three groups by body weight randomly:normal group?1 male,2 female?,lead-exposed at pre-pregnancy group?5male,10 female?and lead-exposed at lactation group?5 male,10 female?.The female mice drank 0.2%lead acetate for 21 days before mating and after procreation respectively for the lead-exposed at pre-pregnancy group and the lead-exposed at lactation group.The rest time and the whole course of the normal group fed free deionized water.After weaning,the offsprings of lead-exposed mothers were divided into five subgroups by body weight randomly?14 each group?:normal saline group,corn oil group,SFN group,VitE group and SFN+VitE group.They were subject to gavage daily at 9 am for four weeks.Gavage doses of VitE and SFN were 30 IU/kg and 25 mg/kg respectively.Meanwhile,14 offsprings of the normal group were chosen as the control group at random.The control group drank lead free deionized water until the behavioral test.The body weights of pups were taken notes once a week during the treatment.The spatial learning and memory ability of them were assessed by the Morris water maze test,and the lead level in the blood were detected by polarography.Superoxide dismutase?SOD?activity and malondialdehyde?MDA?content in hippocampus were measured by the kits.The relative expression levels of amyloid precusor protein?APP?and?-secretase 1?BACE1?in hippocampus tissue were determined by Western Blot.The levels of A?_1-40-40 and A?_1-42-42 in hippocampus were measured by ELISA kit.Results1.Whether in the lead-exposed at pre-pregnancy group or the lead-exposed at lactation group,the mean body weight of mice in subgroup were statistically lower?P<0.05?than the control group.Compared with the control group,a significant increase?P<0.05?of lead level in blood,oxidative stress level in hippocampus,the expression levels of APP,BACE1,A?_1-40-40 and A?_1-42protein were found in the normal saline and corn oil groups.In the Morris water maze test,the mice of the normal saline and corn oil groups performed worse?P<0.05?than the control group.2.The escape latencies,MDA content in hippocampus and the expression levels of APP,BACE1,A?_1-40-40 and A?_1-42protein in the SFN and/or VitE group were significantly decreased?P<0.05?than the lead-exposed group.In addition,compared with the normal saline group,lead level in blood of the mice in SFN group were significantly lower?P<0.05?,but there was no significant difference of SOD activity in the hippocampus?P>0.05?.Compared with the corn oil group,the SOD activity in the hippocampus of the mice in VitE group were significantly raised?P<0.05?,but there was no significant difference of lead level in blood?P>0.05?.In addition,compared with the VitE group,lead level of the mice in SFN and SFN+VitE group were significantly lower?P<0.05?.The activity of SOD of mice in VitE and SFN+VitE groups were higher than that in SFN group?P<0.05?.3.Compared with the lead-exposed at lactation group,there was no significant difference?P>0.05?in escape latency,the number of crossing platform,the level of oxidative stress in the hippocampus and the expression of A?_1-40-40 and A?_1-42-42 in the lead-exposed at pre-pregnancy group.Moreover,the expression of APP and BACE1protein in the lead-exposed at lactation group were higher than that in lead-exposed at pre-pregnancy group?P<0.05?.ConclusionAfter maternal lead exposure at pre-pregnancy and lactation,lead exposure by milk and placenta could increase lead level in blood,affect growth and development as well as cause oxidative damage in hippocampus.As a result,the ability of spatial learning and memory was decreased and the expression of AD-like lesion related protein were increased.Sulforaphane and vitamin E could improve oxidative stress in hippocampus and reduce the level of lead in the blood of the pups.These alterations may contribute to improve the spatial learning and memory decline and retard the development of AD-like lesions.Meanwhile,in the respects of blood lead and oxidative stress,the effect of combined intervention of SFN and vitamin E is better than single intervention.