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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.
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Contributeur : Lilloa Université de Lille <>
Soumis le : jeudi 13 février 2020 - 10:31:23
Dernière modification le : vendredi 16 octobre 2020 - 17:22:16
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Olivier Petrault, Maud Petrault, Thavarak Ouk, Regis Bordet, Vincent Berezowski, et al.. Visceral adiposity links cerebrovascular dysfunction to cognitive impairment in middle-aged mice. Neurobiology of Disease, Elsevier, 2019, Neurobiology of disease, 130, pp.104536. ⟨10.1016/j.nbd.2019.104536⟩. ⟨hal-02477058⟩



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