Background The neurotoxicity of aluminum is characterized by impaired learning and memory, and decreased synaptic plasticity is the main mechanism of the impairment, but associated molecular mechanism is not clear.
Objective This experiment is designed to investigate the effects of subchronic aluminum exposure on the expression of cytoplasmic polyadenylation element binding protein 3(CPEB3) and synaptic plasticity in rat hippocampus.
Methods Forty two-month-old healthy male SD rats were randomly divided into four groups: control group, low-dose aluminum group (10 μmol·kg-1), middle-dose aluminum group (20 μmol·kg-1), and high-dose aluminum group (40μmol·kg-1), with 10 rats in each group. The rats of the aluminum-exposed groups were intraperitoneally injected of 0.1 mL per 100 g body weight maltol aluminum every other day for three months. The rats of the control group were given 0.9% sodium chloride solution. Morris water maze was used to test the learning and memory ability of the rats. The protein expressions of CPEB3, postsynaptic dense protein 95 (PSD95), ionic glutamate receptor 1 (GluR1), ionic glutamate receptor 2 (GluR2), cAMP-response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) were detected by Western blotting. The mRNA expressions of PSD95, GluR1, GluR2, CREB, and BDNF were tested by RT-PCR. The expression of CPEB3 was also determined by immunohistochemistry.
Results The results of Morris water maze showed that the learning and memory ability of the rats exposed to medium and high doses of aluminum were significantly impaired. The escape latencies on the 3rd, 4th, and 5th days in the middle- and high-dose aluminum groups were longer than those in the control group at the same time point (increased by 4.88, 7.24, and 3.92s for the middle-dose group, and 6.41, 9.27, and 6.08 s for the high-dose group, respectively, P < 0.05), the time of staying in target quadrant was shorter (shortened by 13.21 and 16.46 s respectively, P < 0.05), and the times of crossing platform were decreased (reduced by 0.9 and 1.6 times respectively, P < 0.05) on the 6th day. The results of Western blotting showed that the protein expression levels of CPEB3 (0.50±0.06, 0.33±0.07), PSD95 (0.45±0.08, 0.28±0.06), GluR1 (0.38±0.07, 0.31±0.06), GluR2 (0.45±0.08, 0.33±0.09), CREB (0.58±0.11, 0.41±0.07), and BDNF (0.49±0.03, 0.33±0.05) in the hippocampus of the middle- and high-dose groups were lower than those of the control group (1.00±0.00) (P < 0.05). The results of RT-PCR showed that the mRNA expression levels of PSD95, GluR1, GluR2, CREB, and BDNF in the hippocampus of rats exposed to middle and high doses of aluminum were lower than those of the control group (P < 0.05). The immunohistochemical results showed that CPEB3 was mainly expressed in the neuronal cytoplasm of rat hippocampus and decreased with the increase of aluminum concentration.
Conclusion Subchronic aluminum exposure can lead to learning and memory impairment and down-regulation of synaptic plasticity protein in rats, possibly by inhibiting synaptic plasticity-related protein via affecting the expression of CPEB3.
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