The Mechanisms Of Learning And Memory Impairment Induced By Aluminum In Rats And The Improvement Effects Of Gastrodia Elata On The Impairment

[ Objective 1 To study the mechanisms of learning and memory impairment in rat induced by aluminum in vivo and in vitro, to explore the improvement effect of Gastrodia elata on the neurotoxicity induced by aluminum, and to provide the important and scientific basis for the specific prevention of aluminum intoxication and the improvement of aluminum-exposed workers life. [Methods] 1. 36 SD rats, adult and healthy, are divided into 6 groups at random: normal saline, Al3+5mg/kg, Al3+10mg/kg, normal saline + Gastrodia elata, Al3+5mg/kg + Gastrodia elata and Al3+10mg/kg +Gastrodia elata. They are exposed to AlCl3 by intraperitioneal injection at the dose of 0.2ml/d, 60d. Gastrodia elata was administered by drinking water at the dose of 0.4g/kg body weight. After exposure, the step-down test was performed to test the learning and memory abilities of rats, and the changes of pathological state in cerebrum were observed by optical and electron microscope. The aluminum content in brain and some neuro-biochemical items were detected. 2. The expression of GFAP, -APP and SS in aluminum-exposed rats' brain were measured by usingimmno-histochemical method. 3. The nerve cell apoptosis was detected by the technology of situ hybridization. 4. The alteration of mitochondria was measured in cultured nerve cell exposured aluminum. [Results] 1. In Step-down Test, the latency of passive avoidance of rats exposured aluminum shortened significantly (P<0.01) and the number of performing error increased obviously (P<0.01). When the rats were administered Gastrodia elata, the latency prolonged significantly (P<0.01) and the number of performing error decreased obviously (P<0.01). 2.Results of neuroralchemical items show aluminum can make the activities of AChE, MAO-B, SOD and NOS decreased significantly (P<0.01), and it can make the content of NO and Glu decreased significantly (P<0.01) and the content of MDA and GABA increased obviously(P<0.01). The neuroralchemical items of rats exposured both aluminum and Gastrodia elata show Gastrodia elata can make neurotransmitters in normal level except Glu and GABA. 3. The analysis of immno-histochemistry show aluminum can promote the expression of GFAP and -APP of rats' brain significantly (P<0.01) and it can make the number of SS neuron decreased obviously (P<0.01). 4. Aluminum can make the apoptosis index increased significantly (P<0.01). 5. Aluminum can the content of ROS and the death rate of culture nerve cell increased obviously (P<0.01) and make the mitochondria! membrane potential (MPP) and the activities of mitochondrial enzyme decreased significantly (P<0.01). [ Conclusion ] 1. The impairment of learning and memory induced by aluminum is related tothe disorder of the cholinergic system and the monoaminergic system, and the level of LPO. 2. The mitochondria maybe play a important role in the neurotoxicity of aluminum. 3.Gastrodia elata can make the cholinergic system, the monoaminergic system and LPO in order, and it can improve the learning and memory impairment induced by aluminum.