Crosstalk between Peripheral Small Vessel Properties and Anxious-like Profiles: Sex, Genotype, and Interaction Effects in Mice with Normal Aging and 3×Tg-AD mice at Advanced Stages of Disease

Article type: Short Communication

Authors: Jiménez-Altayó, Francesc^{a; b; *} | Sánchez-Ventura, Judith^a | Vila, Elisabet^{a; b} | Giménez-Llort, Lydia^{b; c; *}

Affiliations: [a] Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain | [b] Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain | [c] Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain

Correspondence: [*] Correspondence to: Lydia Giménez-Llort, PhD, Translational Behavioral Neuroscience Lab, Unitat de Psicologia Mèdica, Departament de Psiquiatria i Medicina Legal, Facultat de Medicina, Universitat Autònoma de Barcelona, Avinguda Can Domènech, Edifici M, s/n. Campus Bellaterra, Cerdanyola del Vallès, 08193 Bellatterra, Spain. Tel.: +34 93 581 2378; Fax: +34 93 581 1435; E-mail: [email protected] and Francesc Jiménez-Altayó, PhD, Departament de Farmacologia, Terapèutica i Toxicologia, Facultat de Medicina, Universitat Autònoma de Barcelona, Avinguda Can Domènech, Edifici M, s/n. Campus Bellaterra, Cerdanyola del Vallès, 08193 Bellatterra, Spain. Tel.: +34 93 581 1952; Fax: +34 93 581 1953; E-mail: [email protected].

Abstract: Cardiovascular disease resulting from oxidative stress and inflammation can exacerbate Alzheimer’s disease. This brief report provides the first evidence of compromised small peripheral mesenteric resistance artery (MRA) properties in 15-month-old 3xTg-AD mice. Females showed worse physiologically relevant MRA structural (increased passive external and internal diameters, cross sectional area) and functional (increased active internal diameters) alterations suggesting sex-dependent dysfunctions. At both physiological and high intraluminal pressures, vascular alterations correlated with the anxious-like behavioral profile, in a sex-dependent manner. Finally, the results unveil a crosstalk between peripheral small vessel properties and behavior in both 3xTg-AD mice and age-matched counterparts with normal aging.

Keywords: 3×Tg-AD mice, aging, Alzheimer’s disease, cardiovascular disease, emerging concepts, gender medicine, oxidative stress, peripheral inflammation, small mesenteric resistance arteries, vascular remodeling

DOI: 10.3233/JAD-171019

Journal: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1531-1538, 2018