title: Chronic vascular risk factors (cholesterol, homocysteine, ethanol) impair spatial memory, decline cholinergic neurons and induce blood-brain barrier leakage in rats in vivo.
abstract: Epidemiological studies show that vascular risk factors (e.g. atherosclerosis, diabetes, homocysteine, hypertension or cholesterol) may play a role in the development of Alzheimer's disease. Animal models may help to discover the role of vascular risk factors on cognition. In the present project we treated male Sprague Dawley rats with a diet containing homocysteine (hyperhomocysteinemia) or cholesterol (hypercholesterolemia) for 5 months or exposed the rats to ethanol (20% in drinking water) or a combination of cholesterol+ethanol (mix) for 12 months. Our experiments show that all 3 treatments (homocysteine, cholesterol, ethanol) declined spatial memory in the 8-arm radial maze, reduced the number of cholinergic neurons and induced blood-brain barrier leakage in the cortex. Rats treated with cholesterol also displayed markedly enhanced inflammation in the cortex. Levels of amyloid precursor protein, beta-amyloid((1-42)), as well as tau and phospho-tau 181 were significantly enhanced in the cortex of cholesterol-fed rats. A combination of ethanol and cholesterol did not further potentiate the effects on spatial memory, cholinergic neurons and blood-brain barrier leakage. The data suggest that chronic mild vascular risk factors over months induce small lesions of the brain capillaries in the cortex, which may contribute to the development of vascular dementia or also Alzheimer's disease.
authors: Laboratory for Psychiatry and Exp. Alzheimer's Research, Department of Psychiatry and Psychotherapy, Anichstr. 35, 6020 Innsbruck, Austria.
authors: Daniela
authors: D
authors: Ehrlich
authors: Christian
authors: C
authors: Humpel
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D002784:Cholesterol / Q000009:adverse effects*; D059329:Cholinergic Neurons / Q000473:pathology*; D019587:Dietary Supplements / Q000009:adverse effects; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects*; D006710:Homocysteine / Q000009:adverse effects*; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000150:complications; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000150:complications; D007249:Inflammation / Q000139:chemically induced / Q000150:complications; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D006710:Homocysteine; D000431:Ethanol; D002784:Cholesterol