title: Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice.
abstract: Severe dyslipidemia and the associated oxidative stress could accelerate the age-related decline in cerebrovascular endothelial function and cerebral blood flow (CBF), leading to neuronal loss and impaired learning abilities. We hypothesized that a chronic treatment with the polyphenol catechin would prevent endothelial dysfunction, maintain CBF responses, and protect learning abilities in atherosclerotic (ATX) mice. We treated ATX (C57Bl/6-LDLR(-/-)hApoB(+/+); 3 mo old) mice with catechin (30 mg · kg(-1) · day(-1)) for 3 mo, and C57Bl/6 [wild type (WT), 3 and 6 mo old] mice were used as controls. ACh- and flow-mediated dilations (FMD) were recorded in pressurized cerebral arteries. Basal CBF and increases in CBF induced by whisker stimulation were measured by optical coherence tomography and Doppler, respectively. Learning capacities were evaluated with the Morris water maze test. Compared with 6-mo-old WT mice, cerebral arteries from 6-mo-old ATX mice displayed a higher myogenic tone, lower responses to ACh and FMD, and were insensitive to NOS inhibition (P < 0.05), suggesting endothelial dysfunction. Basal and increases in CBF were lower in 6-mo-old ATX than WT mice (P < 0.05). A decline in the learning capabilities was also observed in ATX mice (P < 0.05). Catechin 1) reduced cerebral superoxide staining (P < 0.05) in ATX mice, 2) restored endothelial function by reducing myogenic tone, improving ACh- and FMD and restoring the sensitivity to nitric oxide synthase inhibition (P < 0.05), 3) increased the changes in CBF during stimulation but not basal CBF, and 4) prevented the decline in learning abilities (P < 0.05). In conclusion, catechin treatment of ATX mice prevents cerebrovascular dysfunctions and the associated decline in learning capacities.
authors.affiliation: Department of Surgery, Montreal Heart Institute Research Center, Université de Montréal, Montreal, Quebec, Canada. eric.thorin@umontreal.ca
authors.forename: Annick
authors.initials: A
authors.lastname: Drouin
authors.forename: Virginie
authors.initials: V
authors.lastname: Bolduc
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thorin-Trescases
authors.forename: Élisabeth
authors.initials: É
authors.lastname: Bélanger
authors.forename: Priscilla
authors.initials: P
authors.lastname: Fernandes
authors.forename: Edward
authors.initials: E
authors.lastname: Baraghis
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lesage
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Gillis
authors.forename: Louis
authors.initials: L
authors.lastname: Villeneuve
authors.forename: Edith
authors.initials: E
authors.lastname: Hamel
authors.forename: Guylaine
authors.initials: G
authors.lastname: Ferland
authors.forename: Eric
authors.initials: E
authors.lastname: Thorin
mesh_terms: D000818:Animals; D053299:Apolipoprotein B-100 / Q000172:deficiency / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D002392:Catechin / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D002537:Intracranial Arteriosclerosis / Q000188:drug therapy*; D007858:Learning / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D053299:Apolipoprotein B-100; D008077:Lipoproteins, LDL; D014280:Triglycerides; D014665:Vasodilator Agents; D002392:Catechin; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester