Effects of Amyloid Precursor Protein Intracellular Domain on Neurogenesis， Learning and Memory in Alzheimer’s Disease Model Mice
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20240907.004
- VernacularTitle:淀粉样前体蛋白胞内结构域对阿尔茨海默病模型小鼠神经发生和学习记忆的影响
- Author:
Mei JIANG
1
;
Xu DENG
1
;
Zixiong QIU
1
;
Xiaojun CUI
1
;
Yuan FU
1
Author Information
1. Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering， School of Basic Medicine，Guangdong Medical University， Dongguan 523808， China
- Publication Type:Journal Article
- Keywords:
amyloid precursor protein intracellular domain;
Alzheimer’s disease;
neurogenesis;
learning and memory;
network pharmacology
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2024;45(5):683-693
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects of amyloid precursor protein intracellular domain （AICD） on neurogenesis， learning and memory in Alzheimer’s disease （AD） model mice. MethodsImmunofluorescence staining was used to detect the proliferation and differentiation of neural progenitor cells （NPCs） cultured in vitro， numbers of neural stem cells and neurons in embryonic cerebral cortex and adult hippocampal dentate gyrus （DG） derived from AICD transgenic mice. The morris water maze was applied to evaluate learning and memory ability of old AICD transgenic mice， and bioinformatics to predict and analyze the underlying molecular mechanisms. ResultsImmunofluorescence staining showed that NPCs， numbers of neural stem cells and neurons in embryonic cerebral cortex and hippocampal DG region were decreased （P < 0.05）， indicating that AICD inhibited neurogenesis in AD model mice at different periods. Morris water maze revealed that AICD increased escape latency of AD model mice， reduced numbers of platform crossing and neuron numbers in DG region （P < 0.05）. Bioinformatics results found 1 723 targets of AICD involved in the regulation of neurogenesis， learning and memory in the pathogenesis of AD， in which the key targets were TP53， CTNNB1， Akt1， EGFR， SRC， EP300， HDAC1， STAT3， HSP90AA1 and MAPK1. KEGG pathway annotation analysis showed that signaling pathways like PI3K-Akt and HIF-1 play a crucial role in the regulation of neurogenesis， learning and memory by AICD. ConclusionsAICD could inhibit hippocampal neurogenesis in AD model mice， thus impair their learning and memory ability， which may be related to PI3K-Akt and HIF-1 signaling pathways. This study provides an experimental basis for further understanding the role of AICD in the pathogenesis of AD.
