Dietary Cholesterol Concentration and Duration Degrade Long-Term Memory of Classical Conditioning of the Rabbit's Nictitating Membrane Response

Abstract

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.

Figure 1

Mean (±SEM) body weight for rabbits in the 0%, 0.5%, 1%, and 2% cholesterol groups upon arrival (Pre) and across the eight weeks of the cholesterol diet.

Figure 2

Mean total serum cholesterol levels at euthanasia for rabbits in the 0%, 0.5%, 1%, and 2% cholesterol groups. ***P < .001.

Figure 3

Mean percent conditioned responding during 10 days of Acquisition and 10 days of tone-alone Extinction separated by 8 weeks on a diet of 0%,  .5%, 1%, or 2% cholesterol added to normal rabbit chow. *P < .05.

Figure 4

Mean (±SEM) body weight for rabbits upon arrival (Pre) and across the eight weeks of their respective diets in the 6CP2, 2PC6, 4C4P, 4P4C, and 0C8P groups where the numbers in the group designation refer to the number of weeks out of eight the rabbits were on either a 2% cholesterol diet (C) or on normal Purina rabbit chow (P). The order of the letters and refers to order in which rabbits received their respective diets.

Figure 5

Mean total serum cholesterol levels at euthanasia for rabbits in the 6CP2, 2PC6, 4C4P, 4P4C, and 0C8P groups. **P < .01, ***P < .001.

Figure 6

Mean percent conditioned responding during 10 days of Acquisition and 10 days of tone-alone Extinction separated by 8 weeks on a specific diet. The 6CP2, 2PC6, 4C4P, 4P4C, and 0C8P group designations refer to the number of weeks out of eight the rabbits were on either a 2% cholesterol diet (C) or on normal Purina rabbit chow (P). The order of the letters and refers to order in which rabbits received their respective diets. *P < .05, **P < .01.