Effect of Programmed Necrosis of Hippocampal Neurons Induced by RIPK1/RIPK3/MLKL Signaling Pathway on Learning and Memory Impairment in Mouse Model of Vascular Dementia
10.3870/j.issn.1672-0741.24.08.014
- VernacularTitle:血管性痴呆小鼠模型通过RIPK1/RIPK3/MLKL信号通路诱导的海马区神经元程序性坏死对其学习记忆障碍的影响
- Author:
Jingjing XU
1
;
Junna KOU
;
Lin XIAO
Author Information
1. 郑州大学第一附属医院病理科,河南省肿瘤病理重点实验室,郑州 450052
- Publication Type:Journal Article
- Keywords:
vascular dementia;
cognitive dysfunction;
necroptosis;
chronic cerebral hypoperfusion;
hippocampus
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(3):357-362
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of hippocampal neuron death,and to explore the relationship between necroptosis of hippocampal neurons and impaired learning and memory in vascular dementia(VaD)mice model.Methods Except the sham group,the mouse model of chronic cerebral hypoperfusion vascular dementia was constructed by bilateral occlusion of the common carotid arteries(2VO).Morris water maze was used to evaluate the cognitive of mice.The mRNA expressions of RIPK1,RIPK3 and MLKL in the hippocampal region of mice was detected by real-time fluorescence quantitative PCR(qPCR).The protein expressions of RIPK1,RIPK3,pRIPK3 and MLKL were detected by Western blotting,and their correlation with the cognitive ability was analyzed.The co-localization of RIPK1,RIPK3 and MLKL was detected by immunofluorescence double labeling.Results qPCR showed that compared with sham group,mRNA expressions of RIPK1,RIPK3 and MLKL in hipp-ocampal neurons in VaD group were significantly increased.Western blot results showed that the protein levels of RIPK1,pRIPK3 and MLKL in hippocampal neuron of VaD group were also significantly increased.The co-expression localization of RIPK1,RIPK3 and MLKL was significantly enhanced in the hippocampus of the mouse model by immunofluorescence double labeling.Further study showed that the expressions of RIPK1,RIPK3 and MLKL were negatively correlated with the target quadrant residence time and the number of platform crossing in the mouse model.Conclusion In the VaD mouse model,the loss of hippocampal neurons and the development of learning and memory dysfunction may be caused by the activation of RIPK1/RIPK3/MLKL signaling pathway,which leads to the programmed necrosis of neurons.
