Effect Of Aluminum Exposure On Cognitive Ability And Expression Of Aβ Gene In Mice

Objective: To explore the effect of chronic aluminum exposure on cognitive ability and expression of Aβgene in mice. Methods: 160 Newly weaned Kunming mouse(male 50 percent) are divided into 4 groups at random.The high.middle and low dose groups were established by the gavages which the dosage of AlCl3 in the fodder are 120,12, and 1.2mg/kg respectively. The control group was foddered regularly. Neurological tests were carried out on the stage of 3 months,6months,9months and 12 months respectively. The spatial learning and memory ability were evaluated by Step Through Test (STT), Step Down Test(SDT) and Morris Water Maze(MWM).Then sudden death the mouse, slices of the cerebral cortex hippocampus was made and morphological changes were observed by optical microscope. Expression ofβ-APP mRNA in brain tissue was detected with methods of real-time fluorescent quantitation. Expression ofβ-APP and Aβprotein in brain tissue were measured with SABC of immunohistoc-hemical method and Western-blot..Results:(1) Learning and memory capability test:①Three months later: compared with control group, the latent period of STT of high dose group was significantly shortened(P<0.05),the latent periods of MWM of high dose group was significantly extended(P<0.05).There were dose-response relationships between aluminum exposure and the latent period of STT(rs=-0.743,P<0.01), of the latent periods of MWM(rs=0.096,P<0.05).②Six months later: compared with control group, the latent period of SDT and STT of high dose groups was significantly shortened(P<0.05),the latent periods of MWM of high dose group was significantly extended(P<0.05).There were dose-response relationships between aluminum exposure and the latent period of STT(rs=-0.590,.P<0.01), of the latent periods of MWM(rs=0.176,P<0.01).③Nine months later: compared with control group, the latent period of SDT of middle and high dose groups was significantly shortened(P<0.05),the error number of SDT of high and middle dose groups was significantly increased(P <0.05); the latent period of STT of middle and high dose groups was significantly shortened(P<0.05); the latent periods of MWM of high dose group was significantly extended(P<0.05). There were dose-response relationships between aluminum exposure and the latent period of SDT(rs=-0.617,P<0.01), the error number of SDT(rs=0.569,P<0.01), the latent periods of STT(rs=-0.558,P<0.01), the latent periods of MWM(rs=0.186,P<0.01).④Twelve months later: compared with control group, the latent period of SDT of middle and high dose groups was significantly shortened(P<0.01),the error number of SDT of high and middle dose groups was significantly increased(P<0.05); the latent period of STT of different dose groups was significantly shortened(P<0.05), the error number of STT of high dose groups was significantly increased(P<0.01); the latent periods of MWM of high,middle and low dose groups was significantly extended(P<0.01), numbers of traversing flat in high and middle dose groups were significantly decreased (P<0.01). There were dose-response relationships between aluminum exposure and the latent period of SDT(rs=-0.740,P<0.01), the error number of SDT(rs=0.679,P<0.01), the latent periods of STT(rs=-0.906,P<0.01), the error number of STT(rs=0.568,P<0.01), the latent periods of MWM(rs=0.229,P<0.01), numbers of traversing flat (rs=-0.661,P<0.01).(2) longitudinal study results:①Control group:compared with 3 months status, the latent period of STT of 12 months was significantly shortened(P<0.05),but no dose-response relationship.②Low dose group: the latent period of STT of 12 months was significantly shortened(P<0.05), the latent periods of MWM was significantly extended(P<0.05). There were dose-response relationships between exposure time and the latent periods of STT(rs=-0.684,P<0.01), the latent periods of MWM(rs=0.334,P<0.01).③Middle dose group:The latent period of SDT of 12 months was significantly shortened (P<0.05), the latent period of STT of 9 and 12 months was significantly shortened (P<0.05), the error number of STT increased (P<0.05), the latent periods of MWM of 12 months extended (P<0.05).There were dose-response relationships between exposure time and the error number of STT (rs=0.672, P<0.01).④High dose group: The latent period of SDT of 9 and 12 months was significantly shortened (P<0.05), the latent period of STT of 9 and 12 months was significantly shortened (P<0.05), the error number of STT increased (P<0.05), the latent periods of MWM of 12 months extended (P<0.05), numbers of traversing flat of 9 and 12 months were significantly decreased (P<0.05).There were dose-response relationships between exposure time and the error number of STT (rs=0.672, P<0.01), the latent periods of MWM(rs=0.667,P<0.01), numbers of traversing flat(rs=0.474,P<0.05).(3)Pathohistology results:in control group the morphosis of mice hippocamp pyramidal layer neuron is basically normal.lining up in order, but with the increasing of the doses of Al3+ exposed, the neurocytes displayed disorderly, the cell junction get loose,, the karyon shrinked, some rings around the neurocyte were observed.(4)Expression ofβ-APP and Aβ:①compared with the control group, on the stage of 12 months the expression ofβ-APP of high dose groups raised obviousiy (P<0.05). There were dose-response relationships between exposure dosage and expression ofβ-APP (rs=0.289, P<0.05).②compared with the control group, on the stage of 9 months the expression ofβ-APP protein (P<0.05) and Aβprotein (P<0.01) of middle and high dose groups raised obviousiy. The expression ofβ-APP protein (P<0.05) and AP protein (P<0.01) of low, middle and high dose groups on the stage of 12 months raised obviousiy. Statistical analysis showed that positive correlations exited between exposure dosage and expression ofβ-APP protein(rs=0.878,P<0.01), Aβprotein (rs=0.738,P<0.01). Conclusion: Aluminium could induce learning and memory disorder in mice, and induce the morphosis changes of mice hippocamp pyramidal layer neurons. The exposure to aluminum could result in the dysfunction of the ability of spatial learning and memory of mice and the over-expression ofβ-APP andβ-AP. It might be one of the most important pathogenic mechanisms.