ABSTRACT
OBJECTIVE: To study the effect of sub-chronic aluminum exposure on synaptic plasticity in the hippocampus of rats and to explore the mechanism of phosphatidylinositol 3 kinase(PI3 K)/protein kinase B(AKT)/rapamycin target protein(mTOR) signaling pathway. METHODS: Specific pathogen free adult healthy male SD rats were randomly divided into control group and low-, medium-and high-dose groups based on body weight, with 10 rats in each group. Rats were treated with maltol aluminum solution at the concentrations of 0, 10, 20 and 40 μmol/kg body weight by intraperitoneal injection, 5 days per week for 3 months. After the exposure, rats were weighed. Morris water maze was used to test the learning and memory ability, and the two-electrode binding technique was used to record the long-term potentiation(LTP) amplitude in the hippocampus CA1 area of rats. The protein expression of PI3 K, AKT and mTOR in rat hippocampus tissues was detected by Western blot. RESULTS: After the exposure, the body weights of rats in the medium-and high-dose groups were lower than that of the control group(P<0.05). The results of the positioning navigation experiment showed that the escape latencies of the rats in the medium-and high-dose groups were shorter than that in the control group during the 2 nd to 4 th days of the experiment(P<0.05). The results of space exploration experiments showed that there was no statistical difference on the target quadrant retention time and the number of crossing the platform among the 4 groups(P>0.05). At 1, 30, and 60 min after high-frequency stimulation, the LTP amplitudes in the hippocampus CA1 area of the aluminum-treated groups were lower than that of the control group at the same time point(P<0.05), and the LTP amplitudes of hippocampus CA1 area of rats decreased with the increase of maltol aluminum exposure dose(P<0.01). The relative expression of PI3 K, AKT and mTOR protein in the hippocampus tissues of the aluminum-treated groups was lower than that of the control group(P<0.05), and the relative expression of the above three proteins decreased with the increase of the maltol aluminum exposure dose(P <0.01). CONCLUSION: Sub-chronic aluminum exposure could lead to dose-dependent inhibition of hippocampus synaptic plasticity in rats, thereby impairing the spatial learning ability of rats. This process may be related to inhibition of PI3 K/AKT/mTOR signaling pathway by aluminum.
ABSTRACT
OBJECTIVE: To observe the effect of maltolate aluminum on synaptic plasticity in the hippocampus of rats and to explore the regulatory effect and mechanism of metabotropic glutamate receptor 1(mGluR1). METHODS: Specific pathogen free healthy adult male SD rats were randomly divided into control group, aluminum group, aluminum agonist group and aluminum antagonist group, 8 rats in each group. The rats in the control group received no treatment; the rats in aluminum group were injected with 5 μL 10 mmol/L maltolate aluminum solution into the lateral ventricle; the rats in aluminum agonists and aluminum antagonist group were injected with 3 μL 10 mmol/L maltolate aluminum solution plus 2 μL 0.1 μmol/L mGluR1 agonist or 2 μL 0.2 μmol/L mGluR1 antagonists into the lateral ventricle, respectively.Maltolate aluminum solution was injected every 2 days and continued for 10 days. After maltolate aluminum exposure, the amplitudes of long-term potentiation(LTP) in hippocampal CA1 region of rats were measured, and the relative expression levels of mRNA and protein of mGluR1, N-methyl-D-aspartate receptor(NMDAR1) and protein kinase C(PKC) in hippocampus tissue of rats were detected by real-time fluorescence quantitative polymerase chain reaction and Western blotting. RESULTS: The amplitude of LTP in hippocampal CA1 region in aluminum group and aluminum agonist group was lower than that in the control group and the aluminum antagonist group(P<0.05). Compared with the control group, the relative expression of mGluR1 mRNA and protein in the aluminum group increased, the relative expression of PKC and NMDAR1 mRNA and protein in the aluminum group decreased(P<0.05). Compared with the aluminum group, the relative expression of mGluR1 mRNA and protein in the aluminum agonist group increased, while the NMDAR1 mRNA decreased(P<0.05); the relative expression of mGluR1 mRNA and protein in the aluminum antagonist group decreased, while the NMDAR1 mRNA and protein increased(P<0.05). Compared with the aluminum agonist group, the relative expression of mGluR1 mRNA and protein decreased, while the NMDAR1 mRNA and protein increased in the aluminum antagonist group(P<0.05). The relative expression level of PKC mRNA and protein in aluminum agonist group and aluminum antagonist group was not statistically significant(P>0.05), and there was no statistical significance in these two groups compared with control group and aluminum group(P>0.05). CONCLUSION: Maltolate aluminum exposure can inhibit synaptic plasticity by inhibiting LTP in hippocampus of rats, and the mechanism may be related to the regulation of NMDAR1 expression by mGluR1.