中国实验动物学报2025，Vol.33Issue(11)：1583-1597,15.DOI:10.3969/j.issn.1005-4847.2025.11.003
用5×FAD小鼠研究神经递质动态变化与淀粉样蛋白沉积及神经炎症的时序关联
Investigating temporal relationships among neurotransmitter dynamics,amyloid deposition and neuroinflammation in the 5×FAD mouse
摘要
Abstract
Objective To investigate temporal relationships among neurotransmitter alterations,amyloid-beta(Aβ)deposition,and neuroinflammation in 5×FAD mice.Methods 5×FAD and C57BL/6J(WT)mice at 1.5 months(early pathological stage),3 months(mid-pathological stage),and 6 months(late pathological stage)were examined to establish a time-window model of Alzheimer's disease(AD)progression.Each age and genotype group included 8 mice.Behavioral phenotyping was assessed using the Y-maze,novel object recognition,and open field tests.Immunofluorescence was used to detect Aβ expression and glial cell activation in the hippocampus and prefrontal cortex(PFC).HE staining was performed to observe hippocampal neuronal morphology.Neurotransmitter levels in the hippocampus and PFC were quantified via high-performance liquid chromatography.Results At 1.5 months,the hippocampal GABA level was lower in AD model group mice than in WT group mice.At 3 months,significant changes in several neurotransmitters,including acetylcholine,glutamate,serotonin,and 5-hydroxyindoleacetic acid(5-HIAA),were detected in the hippocampus of AD model group mice compared with WT group mice.At this stage,minor Aβ deposition and microglial activation were present in both the hippocampus and PFC.By 6 months,neurotransmitter levels further declined in the hippocampus and PFC of AD model group mice,accompanied by extensive Aβ deposition,pronounced hippocampal neuronal damage,and substantial glial cell activation.Cognitive impairments were also observed.Conclusions Neurotransmitter dysregulation in 5×FAD mice emerged by 3 months of age and worsened with disease progression.These alterations were closely associated with Aβ deposition,neuroinflammation,and neuronal injury.关键词
阿尔茨海默病/神经递质/β-淀粉样蛋白/神经炎症Key words
Alzheimer's disease/neurotransmitters/amyloid-beta/neuroinflammation分类
生物科学引用本文复制引用
LIANG Yingying,LI Xin,HOU Xueting,LIU Binglin,LIAN Dingding,CHEN Huan,HOU Hongwei,JI Min..用5×FAD小鼠研究神经递质动态变化与淀粉样蛋白沉积及神经炎症的时序关联[J].中国实验动物学报,2025,33(11):1583-1597,15.基金项目
北京市自然科学基金-大兴创新联合基金重点研究专题项目(L246003),北京生命科技研究院重点科技项目(2023000CB0030,2023100CB0060). Funded by the Beijing Natural Science Foundation-Daxing Innovation Joint Fund Key Research Topic Project(L246003),the Beijing Institute of Life Science and Technology Key Scientific Research Project(2023000CB0030,2023100CB0060). （L246003）
