Abstract
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.
Highlights
Microvasculature disruptions in the brain parenchyma, especially in neocortical and hippocampal subregions, are part of the progressive neurodegeneration in brains of patients withY
There is a 53% increase in average length per capillary in entire hippocampus including principal cell layers (PCL) and white matter in Tg rats (Mann-Whitney U, p ≤ 0.036)
Tg rats show significant within-group differences in average Ncap density between PCL sublayers in Tg rats (Friedman, p ≤ 0.011), with post-hoc confirmation of significantly higher average Ncap density in CA2/3 compared to CA1 (Wilcoxon, p ≤ 0.027) and dentate gyrus (DG) (Wilcoxon, p ≤ 0.027)
Summary
Microvasculature disruptions in the brain parenchyma, especially in neocortical and hippocampal subregions, are part of the progressive neurodegeneration in brains of patients withY. 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. 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. 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). 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.
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