Visceral adiposity links cerebrovascular dysfunction to cognitive impairment in middle-aged mice.

Abstract:

:Midlife cognitive decline is now recognized as a factor of poor prognosis for late-life dementia. Although an epidemiological link has been suggested with high fat diet (HFD)-induced metabolic disorders, the effect of a long period of HFD on midlife cerebrovascular and cognitive functions remains unproven. A cohort of 216 young mice was fed with HFD up to middle age (12 months), and kinetically characterized for metabolic status, including weight, blood lipid profile, hepatic fat accumulation, glucose intolerance, and visceral adiposity. Metabolic disorders were evidenced from 3 months of HFD. Visual recognition memory and flexibility were significantly altered and associated to a visceral adiposity whereas spatial reference memory and working memory did not. Concomitantly, a progressive dysfunction of the vascular endothelium-dependent relaxation was detected in both middle cerebral artery and parenchymal arterioles, with consequences on the regulation of cerebral blood flow, but without any modification of the basal brain tissue MRI perfusion signal. Our data collection empowered us to stratify the mice according to their heterogeneous response to diet, and to propose a statistical prediction model for cognitive impairment, combining visceral adiposity and cerebral vasomotion in a diagnostic perspective of early neurological deficits.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Pétrault O,Pétrault M,Ouk T,Bordet R,Bérézowski V,Bastide M

doi

10.1016/j.nbd.2019.104536

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

104536

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(19)30204-9

journal_volume

130

pub_type

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