%0 Journal Article
%T Dietary Cholesterol Concentration and Duration Degrade Long-Term Memory of Classical Conditioning of the Rabbit¡¯s Nictitating Membrane Response
%A Bernard G. Schreurs
%A Desheng Wang
%A Carrie A. Smith-Bell
%A Lauren B. Burhans
%A Roger Bell
%A Jimena Gonzalez-Joekes
%J International Journal of Alzheimer's Disease
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/732634
%X A rabbit model of Alzheimer¡¯s disease based on feeding a cholesterol diet for eight weeks shows sixteen hallmarks of the disease, including learning and memory changes. Although we have shown 2% cholesterol and copper in water can retard learning, other studies show feeding dietary cholesterol before learning can improve acquisition whereas feeding cholesterol after learning can degrade long-term memory. We explored this issue by manipulating cholesterol concentration and duration following classical trace conditioning of the rabbit¡¯s nictitating membrane response and assessed conditioned responding after eight weeks on cholesterol. First, rabbits given trace classical conditioning followed by 0.5%, 1%, or 2% cholesterol for eight weeks showed body weight and serum cholesterol levels that were a function of dietary cholesterol. Although all concentrations of cholesterol showed some sign of retarding long-term memory, the level of memory retardation was correlated with serum cholesterol levels. Second, rabbits given trace conditioning followed by different durations of a 2% cholesterol diet combined with different durations of a 0% control diet for 8 weeks showed duration and timing of a 2% cholesterol diet were important in affecting recall. The data support the idea that dietary cholesterol may retard long-term memory. 1. Introduction In rabbits fed 2% cholesterol for as little as eight weeks, there are as many as sixteen different indices of pathology that are similar to those seen in Alzheimer¡¯s Disease (AD) including intracellular and extracellular A¦Â, breaches of the blood brain barrier, activation of microglia, apoptosis, increased levels of Apolipoprotein E, phosphorylated tau protein, changes in the cerebrovasculature, and increases in ventricular volume [1¨C12]. Coinciding with these changes in brain pathology, there have been reports of detrimental effects on learning [6, 13¨C16]. Nevertheless, research with this and other animal models suggests that modifying dietary cholesterol can in many cases improve learning and memory. For instance, increasing cholesterol in young DBA/2 mutant mice improves performance on the Morris water maze¡ªa spatial learning task that is normally impaired in this mutant [17, 18]. Feeding cholesterol to young, normal rats also improves performance on the Morris water maze [19]. Feeding cholesterol to rats that are either deficient in cholesterol or have cholesterol synthesis blocked reverses problems with learning and memory [20¨C23]. We have also shown that feeding rabbits cholesterol can facilitate classical
%U http://www.hindawi.com/journals/ijad/2012/732634/