| Objective:(1)To study the effect of subchronic aluminum exposure on learning and memory function in rats.(2)To study the effects of subchronic aluminum exposure on synaptic plasticity in rats through the PI3K/AKT/mTOR signaling pathway.Methods:Sixty adult male SD rats without specific pathogens were selected and divided into four groups,randomly,based on body weight: control group(normal saline),low dose group(10 ?mol/kg maltol aluminum),and medium dose group(20 ?mol/kg maltol aluminum)and high dose group(40 ?mol/kg maltol aluminum).There were 15 rats in each group.The aluminum exposure mode was intraperitoneal injection,and the exposure duration was 3 months.After the exposure,ICP-MS was used to test rat brain aluminum content;Morris water maze was used to monitor rat learning and memory abilities;hippocampal long-term potentiation(LTP)detection technique was used to record the field excitatory postsynaptic potential(fEPSP)in hippocampal CA1 region;Golgi staining was used to observe the morphological changes of nerve cells in the hippocampal CA1 region of rats and count the number of dendritic spines.Western blot was used to determine the expression of PI3 K,AKT and mTOR proteins and their phosphorylated proteins p-PI3 K Tyr467,p-AKT Thr308,p-AKT Ser473 and p-mTOR Ser2448.Results:(1)The results of ICP-MS showed that the aluminum content of rat brain tissue was: control group(0.91 ± 0.09)ng/mg,low dose group(8.92 ± 0.82)ng/mg,medium dose group(20.99 ± 0.94)ng/mg and high dose group(33.69 ± 2.74)ng/mg.With the increase of the exposed dose,the aluminum content of the brain tissue in rats increased.(2)Morris water maze results showed that the average escape latency period of rats in each group was shortened with the increase of training days,and the escape latency period of rats in Al-treated group was prolonged compared with the control group on the same day.The swimming path of rats in each group gradually became clearer and clearer with the increase of training days.With the increase of the dose,the time of rats in each group staying in the target quadrant was gradually shortened,compared with the control group,the time of rats in the medium and high dose groups staying in the target quadrant was statistically shortened(P<0.05).With the increase of the dose,the times of rats crossing the platform decreased gradually.(3)The hippocampal LTP test revealed that all the fEPSPs increased after the highfrequency stimulation in each group,while decreased to some extent after 60 minutes.Compared with the control group,there were statistically significant differences in the low,medium and high dose groups(P<0.05).(4)Golgi staining was used to observe the neurons in hippocampal CA1 area of each group.Axonal bead-like changes were found,and the bead-like changes increased with the increase of the dose.After counting the number of dendritic spines,it was found that the number of dendritic spines decreased with the increase of the dose,which showed a certain dose-response relationship.(5)The western blot results showed that the expression of PI3 K,AKT and mTOR protein increased with the increase of the aluminum exposure dose.Compared with the control group,the expressions of PI3 K,AKT and mTOR protein were significantly increased in each Al-treated group(P<0.05).The expression of p-PI3 K Tyr467,p-AKT Thr308,p-AKT Ser473 and p-mTOR Ser2448 increased with the increase of the dose,and showed a certain dose-response relationship.Compared with the control group,the expression levels of pAKT Thr308 and p-mTOR Ser2448 in the low,medium and high dose groups were statistically increased(P<0.05);compared with the control group,the expression of p-PI3 K Tyr467 protein was statistically increased in the medium and high dose groups(P<0.05);compared with the control group,the expression of p-AKT Ser473 protein in the high dose group was statistically significant(P<0.05).Conclusion:(1)Subchronic aluminum exposure could impair learning and memory in rats.(2)Subchronic aluminum exposure could inhibit LTP in the hippocampus of rats,reduce dendritic spines in nerve cells,and damage synaptic plasticity via activating the PI3K/AKT/mTOR signaling pathway in rats. |
PDF Full Text Request