Comparative Analysis of Neurogenesis and Cerebral Angiogenesis in the Hippocampal Neurogenic Niche in Animals with Two Experimental Models of Alzheimer’s Disease
Introduction. Various animal models are employed to uncover the mechanisms of Alzheimer’s disease (AD) pathogenesis. Understanding brain damage pathogenesis in animal models of neurodegenerative diseases and identifying common patterns inherent to all relevant models is essential for adequate interp...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Research Center of Neurology
2025-06-01
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| Series: | Анналы клинической и экспериментальной неврологии |
| Subjects: | |
| Online Access: | https://annaly-nevrologii.com/pathID/article/viewFile/1227/pdf |
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| Summary: | Introduction. Various animal models are employed to uncover the mechanisms of Alzheimer’s disease (AD) pathogenesis. Understanding brain damage pathogenesis in animal models of neurodegenerative diseases and identifying common patterns inherent to all relevant models is essential for adequate interpretation of findings, development of new models, as well as prevention and therapy strategies.
The study aimed to assess neurogenesis and remodeling of the microvasculature in the subgranular zone (SGZ) of the hippocampal dentate gyrus in mice with two AD models.
Materials and methods. The study employed two in vivo Alzheimer’s disease models: 1) animals with intrahippocampal administration of amyloid-β protein fragment Aβ25–35; 2) 5xFAD transgenic mice. Cognitive functions were evaluated using a passive avoidance test. On days 7 and 28 post-training, we assessed vascular network branching and density in the hippocampus using Evans Blue with subsequent software-based analysis of skeletonized images, analyzed proliferative activity of neuronal and endothelial cells, and their subpopulation composition using BrdU assay and multiparameter immunostaining of brain thin sections.
Results. Animals following intrahippocampal Aβ25 -35 administration demonstrated enhanced neurogenesis and neoangiogenesis over 28 days post-training, unlike 5xFAD mice which showed delayed and less pronounced proliferation of neuronal cells in the SGZ alongside transient increases in proliferating endothelial cells. Both AD models exhibited divergent changes in tip and stalk cell counts within the hippocampal SGZ, indicating non-productive neoangiogenesis confirmed by reduced vascular branching and density in the SGZ of animals from both models.
Conclusion. Cognitive deficits associated with experience-induced neurogenesis and cerebral angiogenesis mechanisms in the hippocampal neurogenic niche differ between AD models representing sporadic and familial variants, highlighting the need for fundamentally different approaches to pathogenetic therapy targeting non-productive angiogenesis and aberrant brain plasticity in various Alzheimer’s type neurodegeneration scenarios. |
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| ISSN: | 2075-5473 2409-2533 |