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Stereological Changes in Microvascular Parameters in Hippocampus of a Transgenic Rat Model of Alzheimer's Disease
Y. Kolinko, L. Marsalova, S. Proskauer Pena, M. Kralickova, PR. Mouton
Language English Country Netherlands
Document type Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
PubMed
34542078
DOI
10.3233/jad-210738
Knihovny.cz E-resources
- MeSH
- Alzheimer Disease pathology MeSH
- Plaque, Amyloid pathology MeSH
- Hippocampus pathology MeSH
- Rats MeSH
- Humans MeSH
- Microvessels * metabolism pathology MeSH
- Disease Models, Animal MeSH
- Rats, Inbred F344 MeSH
- Rats, Transgenic metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
BACKGROUND: Microcirculatory factors play an important role in amyloid-β (Aβ)-related neuropathology in Alzheimer's disease (AD). Transgenic (Tg) rat models of mutant Aβ deposition can enhance our understanding of this microvascular pathology. OBJECTIVE: Here we report stereology-based quantification and comparisons (between- and within-group) of microvessel length and number and associated parameters in hippocampal subregions in Tg model of AD in Fischer 344 rats and non-Tg littermates. METHODS: Systematic-random samples of tissue sections were processed and laminin immunostained to visualize microvessels through the entire hippocampus in Tg and non-Tg rats. A computer-assisted stereology system was used to quantify microvessel parameters including total number, total length, and associated densities in dentate gyrus (DG) and cornu ammonis (CA) subregions. RESULTS: Thin hair-like capillaries are common near Aβ plaques in hippocampal subregions of Tg rats. There are a 53% significant increase in average length per capillary across entire hippocampus (p≤0.04) in Tg compared to non-Tg rats; 49% reduction in capillary length in DG (p≤0.02); and, higher microvessel density in principal cell layers (p≤0.03). Furthermore, within-group comparisons confirm Tg but not non-Tg rats have significant increase in number density (p≤0.01) and potential diffusion distance (p≤0.04) of microvessels in principal cell layers of hippocampal subregions. CONCLUSION: We show the Tg deposition of human Aβ mutations in rats disrupts the wild-type microanatomy of hippocampal microvessels. Stereology-based microvascular parameters could promote the development of novel strategies for protection and the therapeutic management of AD.
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