Back to Search Start Over

Incidence of microvascular dysfunction is increased in hyperlipidemic mice, reducing cerebral blood flow and impairing remote memory.

Incidence of microvascular dysfunction is increased in hyperlipidemic mice, reducing cerebral blood flow and impairing remote memory.

Authors :
Hernandez Torres LD
Rezende F
Peschke E
Will O
Hövener JB
Spiecker F
Özorhan Ü
Lampe J
Stölting I
Aherrahrou Z
Künne C
Kusche-Vihrog K
Matschl U
Hille S
Brandes RP
Schwaninger M
Müller OJ
Raasch W
Source :
Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2024 Feb 26; Vol. 15, pp. 1338458. Date of Electronic Publication: 2024 Feb 26 (Print Publication: 2024).
Publication Year :
2024

Abstract

Introduction: The development of cognitive dysfunction is not necessarily associated with diet-induced obesity. We hypothesized that cognitive dysfunction might require additional vascular damage, for example, in atherosclerotic mice.<br />Methods: We induced atherosclerosis in male C57BL/6N mice by injecting AAV-PCSK9 <superscript>DY</superscript> (2x10 <superscript>11</superscript> VG) and feeding them a cholesterol-rich Western diet. After 3 months, mice were examined for cognition using Barnes maze procedure and for cerebral blood flow. Cerebral vascular morphology was examined by immunehistology.<br />Results: In AAV-PCSK9 <superscript>DY</superscript> -treated mice, plaque burden, plasma cholesterol, and triglycerides are elevated. RNAseq analyses followed by KEGG annotation show increased expression of genes linked to inflammatory processes in the aortas of these mice. In AAV-PCSK9 <superscript>DY</superscript> -treated mice learning was delayed and long-term memory impaired. Blood flow was reduced in the cingulate cortex (-17%), caudate putamen (-15%), and hippocampus (-10%). Immunohistological studies also show an increased incidence of string vessels and pericytes (CD31/Col IV staining) in the hippocampus accompanied by patchy blood-brain barrier leaks (IgG staining) and increased macrophage infiltrations (CD68 staining).<br />Discussion: We conclude that the hyperlipidemic PCSK9 <superscript>DY</superscript> mouse model can serve as an appropriate approach to induce microvascular dysfunction that leads to reduced blood flow in the hippocampus, which could explain the cognitive dysfunction in these mice.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2024 Hernandez Torres, Rezende, Peschke, Will, Hövener, Spiecker, Özorhan, Lampe, Stölting, Aherrahrou, Künne, Kusche-Vihrog, Matschl, Hille, Brandes, Schwaninger, Müller and Raasch.)

Details

Language :
English
ISSN :
1664-2392
Volume :
15
Database :
MEDLINE
Journal :
Frontiers in endocrinology
Publication Type :
Academic Journal
Accession number :
38469142
Full Text :
https://doi.org/10.3389/fendo.2024.1338458