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90Life Research  2019, Vol. 2 Issue (4): 124-136    DOI: 10.12032/life2019-1025-102
Orginal Article     
Age-related changes of senescence-accelerated mouse prone 10 (SAMP10) mice as an animal model for AD
Lei Yu1, Linna Gao1,2, Xue Bai1, Ruomei Che1, Xiaoli He1,3,*()
1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2Hebei North University, Zhangjiakou, China
3Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, China.
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Abstract  

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.



Key wordsSenescence-accelerated mice 10      Alzheimer's disease      Learning and memory impairment      Cholinergic system      Monamine      Amino acid           
Received: 01 October 2019      Published: 14 October 2019
Fund:  This work was supported by the National Natural Science Foundation of China (Grant number: No. 81473586, No. 81202192).
Corresponding Authors: He Xiaoli   
E-mail: hexl2009@163.com
Cite this article:

Lei Yu, Linna Gao, Xue Bai, Ruomei Che, Xiaoli He. Age-related changes of senescence-accelerated mouse prone 10 (SAMP10) mice as an animal model for AD. 90Life Research, 2019, 2(4): 124-136.

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https://www.tmrjournals.com/lr/EN/10.12032/life2019-1025-102     OR     https://www.tmrjournals.com/lr/EN/Y2019/V2/I4/124

Fig. 1 Age-related changes of memory and cognition of SAMP10 mice in behavioral tests.

(A) Changes on the Place Navigation Test in SAMP10 aged 3 months ($\bar{x}$ ± s, n = 12). (B) Changes on the Place Navigation Test in SAMP10 aged 6 months ($\bar{x}$ ± s, n = 12). (C) Changes on the Place Navigation Test in SAMP10 aged 9 months ($\bar{x}$ ± s, n = 12).

Table 1 Age-related changes on the spatial probe test in SAMP10
Table 2 Age-related changes on the step-down passive avoidance test in SAMP1
Fig. 2 Age-related changes of the Cholinergic system in the brain cortex of SAMP10.

(A) Age-related changes on the level of acetylcholine in the cerebral cortex in SAMP10. (B) Age-related changes on the activity of acetylcholin esterase in the cerebral cortex in SAMP10. (C) Age-related changes on the level of choline acetyl transferase in the cerebral cortex in SAMP10. (D) Age-related changes on the level of M-cholinoceptor binding capacity in the cerebral cortex in SAMP10. Note: *P < 0.05, compare with SAMR1, n = 6.

Fig. 3 Age-related changes of the monoamine neurotransmitters in the brain cortex of SAMP10.

(A) Age-related changes on the level of dopamine in the cerebral cortex in SAMP10. (B) Age-related changes on the level of 3,4-dihydroxyphenyl acetic acid in the Cerebral cortex in SAMP1. (C) Age-related changes on the level of homovanillic acid in the cerebral cortex in SAMP10. (D) Age-related changes on the level of 5-HT in the cerebral cortex in SAMP10. (E) Age-related changes on the level of norepinephrine in the cerebral cortex in SAMP10. Note: *P < 0.05, compare with SAMR1, n = 6.

Fig. 4 Age-related changes of the amino neurotransmitters in the brain cortex of SAMP10.

(A) Age-related changes on the level of glutamine in the cerebral cortex in SAMP10. (B) Age-related changes on the level of glutamic acid in the cerebral cortex in SAMP10. (C) Age-related changes on the level of Asp in the cerebral cortex in SAMP10. (D) Age-related changes on the level of γ-aminobutyric acid in the cerebral cortex in SAMP10. (E) Age-related changes on the level of taurine in the cerebral cortex in SAMP10. (F) Age-related changes on the level of glycine in the cerebral cortex in SAMP10. Note: *P < 0.05, compare with SAMR1, n = 6.

Fig. 5 Age-related changes of the hippocampal neurons and Aβ expression in the brain hippocampus of SAMP10.

(A) Nissl staining in CA1 region of the hippocampus (× 400). (B) Nissl staining in CA3 region of the hippocampus (× 400). (C) Aβ of CA1 region in the hippocampus. (D) Aβ of CA3 region in the hippocampus (A: 3-months-old SAMR1. B: 6-months-old SAMR1. C: 9-months-old SAMR1. A1: 3-months-old SAMP10. B1: 6-months-old SAMP10. C1: 9-months-old SAMP10)

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