Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia

Abstract

Evaluation of behavior and cognition in rodent models underpins mechanistic and interventional studies of brain aging and neurodegenerative diseases, especially dementia. Commonly used tests include Morris water maze, Barnes maze, object recognition, fear conditioning, radial arm water maze, and Y maze. Each of these tests reflects some aspects of human memory including episodic memory, recognition memory, semantic memory, spatial memory, and emotional memory. Although most interventional studies in rodent models of dementia have focused on pharmacological agents, there are an increasing number of studies that have evaluated nutritional interventions including caloric restriction, intermittent fasting, and manipulation of macronutrients. Dietary interventions have been shown to influence various cognitive and behavioral tests in rodents indicating that nutrition can influence brain aging and possibly neurodegeneration.

Keywords: aging; calorie restriction; intermittent fasting; macronutrients; memory.

Figure 1

The most commonly used memory behavioral tests in rodents. Notes: (A) Morris water maze: rodent learns to find submerged escape platform over time (black indicates escape platform); (B) Barnes maze: rodent learns to find escape box over time (black indicates escape hole); (C) radial arm water maze: rodent learns the location of the correct arm containing the submerged escape platform (black indicates escape platform); (D) novel object recognition: recognition index calculated as a percentage of time the rodent explores the novel object vs the old object on day 2 (black indicates objects, arrow signifies inter-trial interval); (E) Y maze: number of entries into novel arm quantified after brief training period; and (F) fear conditioning: freezing activity calculated after a brief conditioning phase (lines indicate wires, bolt indicates mild shock). Abbreviations: CR, calorie restriction; IF, intermittent fasting; LPHC, low-protein, high-carbohydrate.