Background Aluminum inhibits hippocampal long-term potentiation (LTP), suggesting that aluminum may impair synaptic plasticity. Neuroligin 1 (NLGN1) can affect the development and maturation of dendritic spines by recruiting N-methyl-D-aspartic acid receptor (NMDAR) and postsynaptic density protein 95 (PSD-95).
Objective The purpose of this study is to investigate the effect of chronic aluminum exposure on hippocampal synaptic plasticity and NLGN1 expression in rats, and reveal the role of NLGN1 in this process.
Methods Forty-eight clean male SD rats were randomly divided into control group, and low, medium, and high dose aluminum groups, with 12 rats in each group. The control group was given normal saline, and the low, medium, and high dose groups were given 10, 20, 40 μmol/kg aluminum-maltolate complexAl(mal)3, respectively. A chronic aluminum exposure model was established by weekly intraperitoneal injection of Al(mal)3 for 5 days and rest for 2 days. The duration of the exposure was 3 months. After the exposure, Morris water maze was used to evaluate escape latency and the number of crossing, indicators of learning and memory function of rats. Field excitatory postsynaptic potential (fEPSP) in CA1 region of hippocampus was measured by LTP assay in vivo. The morphological presentation and number change of dendritic spine of CA1 neurons in hippocampus were detected with Golgi staining. The expressions of hippocampal NLGN1, NMDAR-2A, NMDAR-2B, and PSD-95 were examined by Western blot.
Results As the training days increased, the latencies of the control group and the aluminum exposure groups gradually decreased. Compared with the control group, the latencies of the 20 and 40μmol/kg aluminum exposure groups significantly prolonged in the Morris water maze (on day 2, 3, and 4, 19.67, 5.96, and 6.49s increased of the 20μmol/kg group; 21.77, 10.20, and 9.91 s increased of the 40μmol/kg group; P < 0.05), and the numbers of crossing the original platform decreased by 2.14 times and 3.93 times, respectively (P < 0.05). In 30 min post high frequency stimulation, the fEPSPs of the 20 and 40 μmol/kg aluminum exposure groups were 1.15±0.03 and 1.10±0.06 respectively, and the fEPSPs decreased to 1.03±0.18 and 0.98±0.22 respectively after 60 min, with significant differences compared with the control group (1.41±0.05 and 1.47±0.11, P < 0.05). Compared with the control group(1.302±0.111)/μm, the dendritic spine densities of the 20 and 40 μmol/kg aluminum exposure groups(0.790±0.056), (0.725±0.152)/μm decreased significantly (P < 0.05). After chronic aluminum exposure, compared with the control group (1.00±0.00), the NLGN1 expression levels in the 20 μmol/kg group (0.80±0.07) and in the 40μmol/kg group (0.55±0.05) were reduced significantly (P < 0.05); compared with the control group (1.00±0.00), the expression levels of NMDAR-2A (0.58±0.08), NMDAR-2B (0.56±0.04), and PSD-95 (0.76±0.01) in the 20μmol/kg group were reduced significantly (P < 0.05).
Conclusion Chronic aluminum exposure may impair hippocampal synaptic function by down-regulating NLGN1, NMDAR-2A, NMDAR-2B, and PSD-95 protein expressions, resulting in impaired learning and memory.
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