The Study Of The Dose-effect Relationship On Memory Impairment Induced By Al（mal）₃ In Rats And The Effect Of CAMP-CREB-BDNF Pathway In The Process Of Impairment

Objective:(1) The aim of the present study is to study the dose-effect relationship in Al(mal)3-induced memory impairment.(2) To study the role of c AMP-CREB-BDNF signal pathway in Al(mal)3-induced memory impairment.Methods:1.Animals(1)33 healthy male SD rats were randomly divided into eleven groups:the blank group, the surgery treated group, the saline treated group, the 1 mmol/L Al(mal)3 group, the 2 mmol/L Al(mal)3 group, the 4 mmol/L Al(mal)3 group, the 8 mmol/L Al(mal)3 group, the 16 mmol/L Al(mal)3 group, the 32 mmol/L Al(mal)3 group, the 64 mmol/L Al(mal)3 group, the 128 mmol/L Al(mal)3 group. Each group consist of 3 rats. The blank group did not received any treatment. The other groups were received the intubation in lateral ventricle of brain. The saline treated group was given the saline by intracerebroventricular injection. The other groups were exposed to the corresponding concentration of Al(mal)3 by the injection of intracerebroventricular for 7 days. The aim is to study the dose-effect relationship in Al(mal)3-induced memory impairment.(2)30 healthy male SD rats were randomly divided into five groups: the surgery treated group, the saline treated group, the low dose group(4 mmol/L Al(mal)3), the medium dose group(16 mmol/L Al(mal)3), and the high dose group(64 mmol/L Al(mal)3). Each group consist of 6 rats. The surgery treated group, the saline treated group, the low dose group, the medium dose group, and the high dose group were received the intubation of lateral ventricle. The saline treated group was given the saline by intracerebroventricular injection. The low dose, medium dose, and high dose group were exposed to the corresponding concentration of Al(mal)3 by the injection of intracerebroventricular for 7days. This aim is to study the role of c AMP-CREB-BDNF signal pathway in Al(mal)3-induced memory impairment.2. The field excitatory postsynaptic potential(f EPSP) in CA1 region of hippocamp was recorded by the electrophysiological grapher.3. The expressions of BDNF, Trk B, CREB and PKA-C were detected by the method of western blot.4. The gene expressions of CREB, BDNF were measured by Real-time PCR.5. The content of c AMP was detected by ELISA.Results:1. The results of electrophysiological experiments:(1)Study of dose-effect relationship showed, there was no significant difference of f EPSP between the blank group and the surgery treated group(P>0.05). The hippocampal f EPSP of aluminum treated group was different significantly in all groups(P<0.05)and there was dose-effect relationship between the f EPSP amplitude and exposure dose. The regression curve equation was Y=1.966-0.013X-3.834*10-7*X3.(2) Study of c AMP-CREB-BDNF signal pathway showed that, the hippocampal f EPSP was different significantly among each groups(P<0.05). In addition, compared with the surgery treated group, the hippocampal f EPSP in the medium dose group, and the high dose group were decreased significantly(P<0.05).2. The results of western blot showed that, the protein expressions of BDNF, CREB and PKA-C were different significantly between all groups(P<0.05). The level of the PKA-C in the middle dose group decreased to 75.3 % of the surgery treated group(P<0.05), and the expressions of BDNF, CREB and PKA-C in high dose group decreased to 68.9%(P<0.05)、56.7%(P<0.05)and 67.0%(P<0.05) of the surgery treated group. However, the expression of Trk B protein decreased with the exposed dose increase, but there was no significant difference(P>0.05).3. The results of Real-time PCR showed, the gene expressions of BDNF and CREB were different significantly between different exposure dose(P<0.05). The expressions of BDNF and CREB gene in high dose group decreased 45.8%(P<0.05) and 36.2%(P<0.05) over the surgery treated group, and the expression of BDNF gene in medium dose group also decreased 27.3% over the surgery treated group(P<0.05).4. The results of ELISA showed, the expression of c AMP was different significantly between different dose groups(P<0.05). The expression of c AMP in medium dose group and high dose group decreased 42.2% and 49.8%(P<0.05) over the surgery group.Conclusions:1. The certain dose of Al(mal)3 injected intracerebroventricular could inhibit LTP of hippocampus, and there was dose-effect relationship between f EPSP amplitude and exposure dose.2. The certain dose of Al(mal)3 may cause the impairment of learning and memory in rats, through decreasing the expressions of c AMP-CREB-BDNF related members and CREB and BDNF genes.