Protein Deficiency-Induced Behavioral Abnormalities and Neurotransmitter Loss in Aged Mice Are Ameliorated by Essential Amino Acids
Open Access
- 11 March 2020
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Nutrition
- Vol. 7, 23
- https://doi.org/10.3389/fnut.2020.00023
Abstract
Nutritional epidemiology shows that insufficient protein intake is related to senile dementia. The levels of protein intake in aged people are positively associated with memory function, and elderly people with high protein intake have a low risk of mild cognitive impairment. Although the beneficial roles of protein nutrition in maintaining brain function in aged people are well demonstrated, little is known about the mechanism by which dietary intake of protein affects memory and brain conditions. We fed aged mice a low protein diet (LPD) for 2 months, which caused behavioral abnormalities, and examined the nutritional effect of essential amino acid administration under LPD conditions. The passive avoidance test revealed that LPD mice demonstrated learning and memory impairment. Similarly, the LPD mice showed agitation and hyperactive behavior in the elevated plus maze test. Moreover, LPD mice exhibited decreased concentrations of gamma-aminobutyric acid (GABA), glutamate, glycine, dopamine, norepinephrine, serotonin and aspartate in the brain. Interestingly, oral administration of seven essential amino acids (EAAs; valine, leucine, isoleucine, lysine, phenylalanine, histidine, and tryptophan) to LPD mice, which can be a source of neurotransmitters, reversed those behavioral changes. The oral administration of EAAs restored the brain concentration of glutamate, which is involved in learning and memory ability and may be associated with the observed behavioral changes. Although the details of the link between decreased amino acid and neurotransmitter concentrations and behavioral abnormalities must be examined in future studies, these findings suggest the importance of dietary protein and essential amino acids for maintaining brain function.This publication has 40 references indexed in Scilit:
- Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic miceProceedings of the National Academy of Sciences of the United States of America, 2011
- Glutamate induces de novo growth of functional spines in developing cortexNature, 2011
- Precolumn derivatization reagents for high‐speed analysis of amines and amino acids in biological fluid using liquid chromatography/electrospray ionization tandem mass spectrometryRapid Communications in Mass Spectrometry, 2009
- Frontal and Temporal Dopamine Release during Working Memory and Attention Tasks in Healthy Humans: a Positron Emission Tomography Study Using the High-Affinity Dopamine D2Receptor Ligand [11C]FLB 457Journal of Neuroscience, 2005
- Aspects of spatial memory and behavioral disinhibition in Tg2576 transgenic mice as a model of Alzheimer’s diseaseBehavioural Brain Research, 2005
- Prevalence of Dysphagia Among Community-Dwelling Elderly Individuals as Estimated Using a Questionnaire for Dysphagia ScreeningDysphagia, 2004
- Transgenic mice expressing the βAPP695SWE mutation: effects on exploratory activity, anxiety, and motor coordinationBrain Research, 2003
- Age-related changes in the uptake and release of glutamate and aspartate in the mouse brainMechanisms of Ageing and Development, 1995
- Tryptophan and nutritional status of patients with senile dementiaPsychological Medicine, 1986
- Neurotransmitter and carbohydrate metabolism during aging and mild hypoxiaNeurobiology of Aging, 1981