The Change Trend And Daily Content Of Amino Acids In Mice Brain And The Effect Of Chrysophanol On The Content Of Amino Acids In The Brain Of AD Model Mice

There is an amino acid（AA）neurotransmitter in the brain,excitatory amino acids（EAA）and inhibitory amino acid（IAA）neurotransmitters.The balance between these neurotransmitters can maintain the function of the human brain.Excitatory amino acid neurotransmitters mainly include aspartic acid（Asp）and glutamate（Glu）;inhibitory amino acid neurotransmitters mainly include gamma-aminobutyric acid（GABA）and glycine（Gly）.The pathogenesis of Alzheimer’s disease（AD）is very complicated.Decreased learning and memory ability is the main manifestation of AD.In recent years,many studies have shown that learning and memory ability is closely related to amino acid neurotransmitters.Chrysophanol is a purified active ingredient in rhubarb anthraquinones.Studies have shown that chrysophanol has anti-inflammatory,antioxidant,and neuroprotective effects.Many studies have shown that chrysophanol has preventive or therapeutic effects on AD.In this experiment,for the first time,the changes of Glu,Asp,GABA,and Gly contents(μg·mg^-1)in the brains of 4～9 weeks old KM mice within24 hours were continuously measured over time.Modeling experiment,a single intracerebroventricular injection of Aβ_25-35 was used to prepare AD model mice to study the effect of chrysophanol on the contents of Glu,Asp,GABA,and Gly in the brain of AD model mice.Kunming（KM）mice were divided into 7 groups:blank control group,sham operation group,model group,piracetam group,chrysophanol 10 mg·kg^-1 dose group,chrysophanol1 mg·kg^-1 dose group,chrysophanol 0.1 mg·kg^-1 dose group.The blank control and sham operation had 8 rats in each group,and the other groups had 12 rats in each group.After the model was made,the drug was administered continuously for 14 days,and the content of the four amino acids in the cortical amino acid samples was detected by the automatic amino acid analyzer method.The jumping platform experiment was used to test the changes of learning and memory ability in mice.The experimental results showed that the contents of 4 amino acids in the cortex of 4～9 weeks old mice fluctuated regularly within 24 hours.The results showed that the contents of Glu and Asp in 4～9 weeks old mice are higher at 19～3 o’clock,lower at 7 o’clock;GABA and Gly content are lower at 3 o’clock,higher at 7 o’clock;Glu/GABA ratio changes constantly,with a downward trend at 4～5 weeks,and relatively stable changes at 5～8weeks,8～9 weeks is on the rise.The difference in the content of 4 amino acids in the cortex of 4～9 weeks old mice at 7 and 19 o’clock showed that the Glu content was higher at 19 o’clock,and the difference in mice aged 4,6,and 9 weeks was significant（P<0.05）;Asp at 19 o’clock content is higher,among which the difference between 4,8,and 9 weeks old mice is more obvious（P<0.05）;the GABA content is higher at 7,and the difference is more obvious in 5,7,8,and 9 weeks old mice（P<0.05）;The difference in Gly content is not obvious.The results of the detection of excitatory amino acids and inhibitory amino acids at 24 time points in 9 weeks old mice showed that the content of Glu and Asp reached the highest peak at 19o’clock and the lowest peak at 8 o’clock;GABA content reached the highest peak at 7 o’clock and 1 o’clock.The lowest peak is reached;the Gly content reaches the highest peak at 9 o’clock and the lowest peak at 22 o’clock;the Glu/GABA ratio is relatively low at 5～11,and relatively high at the rest of the time.Before the administration of chrysophanol,there was no significant difference in the body weight of the mice in each group.After the administration,the body weight of the mice in the model group was lower than the other groups.Compared with the model group,the body weight of the mice in each administration group was significantly increased（P<0.05）.The results of the platform jumping experiment showed that compared with the sham operation group,the mice in the model group increased the number of errors and the latency time was shortened.Compared with the model group,the mice in each administration group decreased the number of errors and the latency time increased significantly（P<0.05）.The cortical amino acid test results showed that compared with the sham operation group,the Glu content and Glu/GABA ratio of the model group increased,and the Asp,Gly and GABA content decreased;compared with the model group,the piracetam group and chrysophanol 10,1 mg·kg^-1 group Glu content and Glu/GABA ratio decreased,chrysophanol 10 mg·kg^-1 group Asp content increased,piracetam group and chrysophanol 10,1 mg·kg^-1group Gly The content of GABA and GABA increased（P<0.05）.In summary,the contents of 4 amino acids in 4～9 weeks old mice fluctuate continuously within 24 hours and show regular changes.The balance of excitatory amino acids and inhibitory amino acids can maintain the normal physiological activities of mice;chrysophanol can significantly reduce Aβ_25-35 The number of errors caused by AD model mice,prolonging the reaction time,and improving the learning and memory ability of AD mice;Chrysophanol can normalize the function of neurons in the brain by regulating the content of excitatory amino acids and inhibitory amino acids in the brain.Thereby improving the symptoms of Alzheimer’s disease.