Low Protein Diet Induces Memory Loss and Anxiety Like Behavior via Decreases of Neurotransmitters in Aged Male Mice (P14-028-19)

Abstract

ObjectivesIncrease of elderly people, dementia and cognitive decline has been already one of the social problems all over the world. There are a lot of risk factors including dietary composition. Several studies have reported the importance of protein for maintaining brain functions in the elderly, but the details are not well understood. To clarify the relationship between protein intake and brain function in the elderly, we evaluated the effect of low protein diet on cognitive function and psychiatric symptoms in aged mice. MethodsMale mice at 60 weeks of age were fed a control diet (NPD; casein 20%) or a low protein diet (LPD; casein 5%). To evaluate neurobehavioral abnormality, we performed the elevated plus maze task (Day 64) and Passive avoidance task (conditioning: Day 66, evaluation: Day 67). Cerebral cortex tissues and plasma were measured for free amino acid concentration by LC-MSMS method, and monoamine concentration in cerebral cortex was measured by HPLC method. ResultsIn the Passive avoidance task, LPD group decreased the time to keep staying in the light box and the rate of individuals entering the dark box during the test period. In the elevated plus maze task, LPD group significantly increased in the number of entry and staying times in open arm. In addition, total travel distance was significantly increased. Moreover, LPD decreased the concentration of not only amino acid in plasma and cerebral cortex but also neurotransmitter such as Glutamate, GABA, Aspartate, Glycine, Dopamine, Norepinephrine, Serotonin. ConclusionsWe found that long-term intake of low-protein diet occurred memory loss and anxiety like behavior in elderly mice. Intracerebral neurotransmitters are mainly synthesized from amino acids, which is transferred from blood, within the brain. Therefore, behavioral change observed in LPD group might be induced by the decrease of neurotransmitters in the brain. Funding SourcesAjinomoto Co., Inc.