Stereological Changes in Microvascular Parameters in Hippocampus of a Transgenic Rat Model of Alzheimer's Disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F21%3A10432358" target="_blank" >RIV/00216208:11140/21:10432358 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kqiE.nQs-S" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kqiE.nQs-S</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3233/JAD-210738" target="_blank" >10.3233/JAD-210738</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Stereological Changes in Microvascular Parameters in Hippocampus of a Transgenic Rat Model of Alzheimer's Disease

Popis výsledku v původním jazyce

Background: Microcirculatory factors play an important role in amyloid-β (Aβ)-related neuropathology in Alzheimer&apos;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&lt;=0.04) in Tg compared to non-Tg rats; 49% reduction in capillary length in DG (p&lt;=0.02); and, higher microvessel density in principal cell layers (p&lt;=0.03). Furthermore, within-group comparisons confirm Tg but not non-Tg rats have significant increase in number density (p&lt;=0.01) and potential diffusion distance (p&lt;=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.

Název v anglickém jazyce

Stereological Changes in Microvascular Parameters in Hippocampus of a Transgenic Rat Model of Alzheimer's Disease

Popis výsledku anglicky

Background: Microcirculatory factors play an important role in amyloid-β (Aβ)-related neuropathology in Alzheimer&apos;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&lt;=0.04) in Tg compared to non-Tg rats; 49% reduction in capillary length in DG (p&lt;=0.02); and, higher microvessel density in principal cell layers (p&lt;=0.03). Furthermore, within-group comparisons confirm Tg but not non-Tg rats have significant increase in number density (p&lt;=0.01) and potential diffusion distance (p&lt;=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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/EF16_019%2F0000787" target="_blank" >EF16_019/0000787: Centrum výzkumu infekčních onemocnění</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Alzheimer&apos;s Disease

ISSN

1387-2877

e-ISSN

—

Svazek periodika

84

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

249-260

Kód UT WoS článku

000722639900020

EID výsledku v databázi Scopus

2-s2.0-85121405391