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Defective hippocampal neurogenesis underlies cognitive impairment by carotid stenosis-induced cerebral hypoperfusion in mice

Authors :
Enrique Fraga
Violeta Medina
María Isabel Cuartero
Alicia García-Culebras
Isabel Bravo-Ferrer
Macarena Hernández-Jiménez
Juan Manuel Garcia-Segura
Olivia Hurtado
Jesus Miguel Pradillo
Ignacio Lizasoain
María Ángeles Moro
Source :
Frontiers in Cellular Neuroscience, Vol 17 (2023)
Publication Year :
2023
Publisher :
Frontiers Media S.A., 2023.

Abstract

Chronic cerebral hypoperfusion due to carotid artery stenosis is a major cause of vascular cognitive impairment and dementia (VCID). Bilateral carotid artery stenosis (BCAS) in rodents is a well-established model of VCID where most studies have focused on white matter pathology and subsequent cognitive deficit. Therefore, our aim was to study the implication of adult hippocampal neurogenesis in hypoperfusion-induced VCID in mice, and its relationship with cognitive hippocampal deficits. Mice were subjected to BCAS; 1 and 3 months later, hippocampal memory and neurogenesis/cell death were assessed, respectively, by the novel object location (NOL) and spontaneous alternation performance (SAP) tests and by immunohistology. Hypoperfusion was assessed by arterial spin labeling-magnetic resonance imaging (ASL-MRI). Hypoperfused mice displayed spatial memory deficits with decreased NOL recognition index. Along with the cognitive deficit, a reduced number of newborn neurons and their aberrant morphology indicated a remarkable impairment of the hippocampal neurogenesis. Both increased cell death in the subgranular zone (SGZ) and reduced neuroblast proliferation rate may account for newborn neurons number reduction. Our data demonstrate quantitative and qualitative impairment of adult hippocampal neurogenesis disturbances associated with cerebral hypoperfusion-cognitive deficits in mice. These findings pave the way for novel diagnostic and therapeutic targets for VCID.

Details

Language :
English
ISSN :
16625102
Volume :
17
Database :
Directory of Open Access Journals
Journal :
Frontiers in Cellular Neuroscience
Publication Type :
Academic Journal
Accession number :
edsdoj.70bfd65a6b34e31a916d9dd24755df3
Document Type :
article
Full Text :
https://doi.org/10.3389/fncel.2023.1219847