| Lead is well known as a toxicant that can affect the function of many organs,especially the nervous system with low-level lead exposure perennially. The infancyis particularly sensitive to lead because of the BBB (Blood Brain Barrier) of infancyis not mature. Lead can affect developing brain by impacting cognition, memory, andbehavioral control due to its great bioaccumulation. Beta-amyloid precursor protein(APP) is closely related to learning and memory ability, and altered proteolyticprocessing of it may increase the level of amyloid beta-peptide (Aβ), which can resultin neurons and learning and memory ability impairment. Studies in rodents havedemonstrated that lead exposure may participate in this process, and the accumulationof Aβ is a causal factor and key link to AD pathogenesis.ObjectivesTo investigate the effects of different lead exposure on spatial learning andmemory ability and the expression of APP protein in mice hippocampus. And explorethe potential mechanism of lead nurotoxity by analysing the correlation betweenspatial learning and memory ability and APP protein expression.MethodsThere were48weaning male mice (21day) divided into four groups randomly.Lead acetate was administered in drinking water in low, modrate and high-levelexposure groups at the dosages of2g/L,4g/L, and6g/L respectively. The controlgroup was fed distilled water. The weights of mice were record once a month. Afterthree months, the spatial learning and memory ability were evaluated by Morris watermaze (MWM). We analyzed the escape latency of the first four days and the times ofacross platform of the last day. Two days after MWM, narcotize the mice, three wholebrains in every groups were collected to do immunohistochemistry test, and the otherhippocampi were separated to two departments, one for determining the concentrationof lead by using graphite furnace atomic absorption spectrometry, as well as wholeblood; another for measured the expression of APP protein by Western Blot. ResultsThe weights of mice: the weight of modrate and high-level groups were decreasethan control group(P<0.01),and these two groups were also decrease than low-levelgroup (P<0.05).Results of MWM: at first four days, compared with the control group, the groupsexposed to lead were significantly long (P<0.05), and high-level group was longerthan other exposed groups (P<0.05). On the6thday, the times of across platform ofdifferent dose groups were significantly less than control group (P<0.01).The lead levels in blood and hippocampus: the lead levels in blood andhippocampus were higher in all of lead exposure groups than control group (P<0.01),the lead levels of modrate and high-level groups were significantly higher thanlow-level group (P<0.05).The results of immunohistochemistry: the APP protein was mainly located in thecytoplasm. The Average density of APP protein in CA1area of mouse pups in threelead exposure groups were higher than that in the control group (P<0.01), andmodrate and high-level groups were significantly increased than low-level group(P<0.01).The results of Western Blot: the protein levels of APP in the exposure groupswere significantly enhanced compared with the control group (P<0.05). Andmodrate-level and high-level group were significantly increased than low-level group(P<0.05).The results of correlation analysis: the spatial learning and memory performancewas related with lead levels of blood and hippocampus (P<0.01); the expression ofAPP protein was positively related with lead levels (P<0.01) and negatively relatedwith learning and memory ability (P<0.01).Conclusion(1) Lead exposure to young mice can decrease the mice body weights, and leadexposure results in a significant lead accumulation of blood and hippocampus.(2) Lead exposure to young mice impacts their MWM performance, and damagethe ability of spatial learning and memory.(3) Lead exposure to young mice results in the over-expression of APP protein inmice hippocampus, which could be responsible for the disfunction of the ability of spatial learning and memory. This might be one of the pathogenic mechanisms of leadtoxicity on neuron. |
PDF Full Text Request