Chronic Aluminum Exposure On Rat Hippocampal Ltp And Its Mechanism

Objective:Neural electrophysiology, biology and other detection methods were applied to observe rats'changes after chronic aluminum exposure in learning and memory behavior, hippocampal long-term potentiation (LTP), extracellularsignal-regulated kinase (ERK) protein and ERK mRNA expression, with the objective to investigate the effect mechanisms of different doses of aluminum exposure on rat learning and memory and to provide experimental evidence for "Mind in the Brain" theory in traditional Chinese medicineMaterial and method:1.Experimental animals and groupingThirty weaned male Wistar rats, weighing 30±5g, were randomly divided into 3 groups of 10 rats:control group (given distilled water), low-dose group (given 0.3% AlCl3 aqueous solution prepared with distilled water), and high dose group (given 0.6% AlCl3 aqueous solution prepared with distilled water). Rats in each group have drunk the given liquid continuously by free drinking for 40 days. Inside the animal lab, the temperature ranged from 20 to 23℃and relative humidity kept in the range from 50-55%. The rats were provided by Laboratory Animal Centre, Liaoning University of Traditional Chinese Medicine, Shenyang, China.2.Behavioral observationThe rats'behaviors of learning and memory performance in a circular Morris water maze have been watched continuously for 5 days.3. Electrophysiological observationExtracellular microelectrode was taken to record rats'hippocampal DG-CA3 pathway of LTP (long-term potentiation), and population spike (PS) in each group.4. RT-PCRRT-PCR was taken to test the rats'extracellular signal-regulated kinase (ERK) mRNA expression in each group.5.ProteinWestern blot was taken to measure the rats'extracellular signal-regulated kinase (ERK) activity and content changes in each group.Results:1.Behaviors Comparing with the control group in the behavior performance study in learning and memory in water maze, the rats in both the low-dose group and the high dose group spent more time in finding platform water, and there is significant difference (p<0.05). While compared with the low-dose group, the rats in the high-dose group spent more time in finding platform, and there is significant difference (p<0.05).2. Electrical changeComparing with the control group, the rats'increased LTP on hippocampal DG-CA3 pathway population spikes (PS) amplitude ratio gradually decreased in both the low-dose group and the high-dose group with increased doses of aluminum exposure. There is significant difference (p<0.05).3.Gene expressionComparing with the control group, the rats in both the low-dose group and high-dose group reduced ERK mRNA expression, and there is significant difference (p<0.05).4.Protein expressionComparing with the control group, the rats in both the low-dose group and the high-dose group reduced ERK Western-Blot expression, and there is significant difference (p<0.05).Conclusion:1. Chronic aluminum exposure resulted in rats'memory decline and was in a dose-dependent relationship.2. Chronic aluminum exposure caused the increased PS (population spike) amplitude LTP ratio decline gradually.3. Chronic aluminum exposure caused the mRNA expression of ERK reduce significantly.4. Chronic Aluminum Exposure enabled ERK protein expression to decrease significantly.