Song Jing, Liu Ying, Zhang Hui Fang, Zhang Qin Li, Niu Qiao
Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
Biomed Environ Sci. 2014 Feb;27(2):77-84. doi: 10.3967/bes2014.006.
To explore the effects of exposure to aluminum (Al) on long-term potentiation (LTP) and AMPA receptor subunits in rats in vivo.
Different dosages of aluminum-maltolate complex [Al(mal)3] were given to rats via acute intracerebroventricular (i.c.v.) injection and subchronic intraperitoneal (i.p.) injection. Following Al exposure, the hippocampal LTP were recorded by field potentiation technique in vivo and the expression of AMPAR subunit proteins (GluR1 and GluR2) in both total and membrane-enriched extracts from the CA1 area of rat hippocampus were detected by Western blot assay.
Acute Al treatment produced dose-dependent suppression of LTP in the rat hippocampus and dose-dependent decreases of GluR1 and GluR2 in membrane extracts; however, no similar changes were found in the total cell extracts, which suggests decreased trafficking of AMPA receptor subunits from intracellular pools to synaptic sites in the hippocampus. The dose-dependent suppressive effects on LTP and the expression of AMPA receptor subunits both in the membrane and in total extracts were found after subchronic Al treatment, indicating a decrease in AMPA receptor subunit trafficking from intracellular pools to synaptic sites and an additional reduction in the expression of the subunits.
Al(mal)3 obviously and dose-dependently suppressed LTP in the rat hippocampal CA1 region in vivo, and this suppression may be related to both trafficking and decreases in the expression of AMPA receptor subunit proteins. However, the mechanisms underlying these observations need further investigation.
探讨体内暴露于铝(Al)对大鼠长时程增强(LTP)及α-氨基-3-羟基-5-甲基-4-异唑丙酸(AMPA)受体亚基的影响。
通过急性脑室内(i.c.v.)注射和亚慢性腹腔内(i.p.)注射给予大鼠不同剂量的苹果酸铝络合物[Al(mal)3]。铝暴露后,采用场电位技术在体内记录海马LTP,并通过蛋白质免疫印迹法检测大鼠海马CA1区总提取物和膜富集提取物中AMPA受体亚基蛋白(GluR1和GluR2)的表达。
急性铝处理导致大鼠海马LTP呈剂量依赖性抑制,膜提取物中GluR1和GluR2呈剂量依赖性降低;然而,在总细胞提取物中未发现类似变化,这表明海马中AMPA受体亚基从细胞内池向突触位点的转运减少。亚慢性铝处理后,发现对LTP以及膜提取物和总提取物中AMPA受体亚基表达均有剂量依赖性抑制作用,表明AMPA受体亚基从细胞内池向突触位点的转运减少,且亚基表达进一步降低。
Al(mal)3在体内明显且剂量依赖性地抑制大鼠海马CA1区的LTP,这种抑制可能与AMPA受体亚基蛋白的转运及表达降低有关。然而,这些观察结果背后的机制需要进一步研究。