Abstract:
Background Aluminum is environmentally abundant in our biosphere and an identified neurotoxicant. A number of studies have shown that aluminum damages long-term potentiation (LTP) in the hippocampus of rats, but the mechanism is not clear.
Objective This in vivo experiment investigates the effects of subchronic aluminum exposure on postsynaptic density protein 95 (PSD95) and LTP in the hippocampus of rats.
Methods Twenty-four healthy Sprague-Dawley male rats were randomly divided into control group, low-dose aluminum group, medium-dose aluminum group, and high-dose aluminum group according to body weight, with six rats in each group. Via intraperitoneal injection every two days, the control group was administered with saline, and the aluminum groups were injected with 10, 20, or 40 μmoL/kg Al(mal)3 for 12 weeks. The field excitatory post-synaptic potential (fEPSP) in CA1 region was recorded by field potentiation technique in vivo. The hippocampal PSD95 protein relative expression was examined by Western blotting. The level of palmitoylated PSD95 was determined by immunoprecipitation-acyl biotin replacement.
Results The LTP results in CA1 region in hippocampus of rats showed that the amplitudes of fEPSP in each group were similar at baseline (P>0.05), but different at 1, 30, and 60 min after high-frequency stimulation (P < 0.05). At 1 min and 60 min, the amplitudes of the low-, medium-, and high-dose groups were lower than those of the control group (P < 0.05), the amplitudes of the medium-and highdose groups were lower than those of the low-dose group (P < 0.05), and the amplitude of the high-dose group was lower than that of the medium-dose group (P < 0.05). At 30 min, the amplitudes of the low-, medium-, and high-dose groups were lower than that of the control group (P < 0.05), and the amplitudes of the medium-and high-dose groups were lower than that of the low-dose group (P < 0.05). The Western blotting results showed that the relative expression levels of PSD95 of the low-, medium-, and high-dose groups were 0.84±0.08, 0.76±0.17, and 0.68±0.19, respectively, lower than that of the control group (1.00±0.00) (P < 0.05). The results of immunoprecipitationacyl biotin replacement showed that the palmitoylation levels of PSD95 protein in the control group and the low-, medium-, and highdose groups were 0.66±0.20, 0.55±0.11, 0.37±0.11, and 0.36±0.15, respectively; the palmitoylation levels of PSD95 protein in the medium-dose and high-dose groups were lower than that in the control group (P < 0.05).
Conclusion Subchronic aluminum exposure could lead to decreased expression of PSD95 protein and palmitoylation in rat hippocampus, which may be one of the mechanisms of impaired LTP induced by aluminum.
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