摘要
Background: To explore the influence of age-related changes in learning and memory capacity of SAMP10, an Alzheimer's disease (AD) model mice, and provide theoretical foundation for the selection of month age in related experiment. Methods: SAMP10 female mice with the age of 3, 6 and 9 months were used as the objects of experiment, while the age-matched female SAMR1 were used as the controls, with 12 in each group. The learning memory capacity of mice at different age was detected through Morris water maze and step-down passive avoidance test;meanwhile, the acetylcholine, acetylcholinesterase, choline acetyltransferase, and M-cholinergic receptor binding capacity levels were determined to detect the cholinergic system damage degree in mice with different month age. In addition, the contents of monoamine neurotransmitters such as dopamine, 3,4-dihydroxyphenyl acetic acid, homovanillic acid, norepinephrine and 5-HT, as well as those of amino acid transmitters such as glutamic acid, glutamine, aspartic acid,γ-aminobutyric acid, taurine and glycine in the brain cortex were detected by high performance liquid chromatography-electrochemical deposition. Besides, changes in hippocampal neurons were observed through Nissl staining, and the changes of Aβ in hippocampal CA1 and CA2 regions of SAMP10 were also detected by immunohistochemistry so as to explore the effects of age on the memory capacity of SAMP10. Results: It was discovered in the behavior test and AD-related index tests that: there was no significant difference between the age-matched SAMR1 and the SAMP10 at the age of 3 and 6 months. But the 9-months-old mice suffered remarkable senescence characteristics, including obviously declined learning memory capacity;down-regulated neurotransmitter levels, enzyme activities and amino acid expression;reduced hippocampal neuron number;and increased deposition of hippocampal Aβ protein. Conclusion: It is discovered in this study through behavior tests and AD-related indexs detection that, the learning memory capacity of SAMP10 shows age-dependence, which is gradually decreased with the increase of age, and the 9-months-old mice have developed marked memory impairment and senescence characteristics. SAMP10 is the recognized AD model, the appropriate month age for preventive medication is about 7 months, while that for therapeutic medication is 8-9 months.
基金
the National Natural Science Foundation of China (Grant number:No.81473586,No.81202192).
