Dietary branched chain amino acids ameliorate injury-induced cognitive impairment
Open accessAbstract
Neurological dysfunction caused by traumatic brain injury results in profound changes in net synaptic efficacy, leading to impaired cognition. Because excitability is directly controlled by the balance of excitatory and inhibitory activity, underlying mechanisms causing these changes were investigated using lateral fluid percussion brain injury in mice. Although injury-induced shifts in net synaptic efficacy were not accompanied by changes in hippocampal glutamate and GABA levels, significant reductions were seen in the concentration of branched chain amino acids (BCAAs), which are key precursors to de novo glutamate synthesis. Dietary consumption of BCAAs restored hippocampal BCAA concentrations to normal, reversed injury-induced shifts in net synaptic efficacy, and led to reinstatement of cognitive performance after concussive brain injury. All brain-injured mice that consumed BCAAs demonstrated cognitive improvement with a simultaneous restoration in net synaptic efficacy. Posttraumatic changes in the expression of cytosolic branched chain aminotransferase, branched chain ketoacid dehydrogenase, glutamate dehydrogenase, and glutamic acid decarboxylase support a perturbation of BCAA and neurotransmitter metabolism. Ex vivo application of BCAAs to hippocampal slices from injured animals restored posttraumatic regional shifts in net synaptic efficacy as measured by field excitatory postsynaptic potentials. These results suggest that dietary BCAA intervention could promote cognitive improvement by restoring hippocampal function after a traumatic brain injury.
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In an animal model of TBI, BCAA supplementation improved cognition in rats following lateral fluid percussion injury.
“Using an animal model of TBI, Cole et al. (2010) reported improved cognition in rats supplemented with BCAAs following lateral fluid percussion injury.”
From Alzheimer’s disease: Targeting the glutamatergic system (2020) · cites this paper as Cole et al. 2010
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- Authors
- Cole, J. T., Mitala, C. M., Kundu, S., Verma, A., Elkind, J. A., Nissim, I., & Cohen, A. S.
- Affiliations
- Division of Neurology and
- Children's Hospital of Philadelphia (US)
- Uniformed Services University of the Health Sciences (US)
- Johns Hopkins University (US)
- Corresponding author
- Cohen, Akiva S.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-12-29
- Volume
- 107
- Issue
- 1
- Pages
- 366-371
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2806733
- OpenAlex
- W2135865446
- Cited by
- 148
- References
- 28
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 10 · 2023: 14 · 2022: 14 · 2021: 6 · 2020: 12 · 2019: 11 · 2018: 9 · 2017: 9 · 2016: 12 · 2015: 5 · 2014: 8 · 2013: 6 · 2012: 5
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Update notices
- correction (2010-02-02)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK053761)
- National Institute of Neurological Disorders and Stroke (R01NS069629, T32NS043126)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD059288)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- branched-chain amino acids, traumatic brain injury, cognitive impairment, excitation-inhibition balance, hippocampus, glutamate synthesis, GABA, lateral fluid percussion injury, dietary intervention, branched-chain amino acid aminotransferase, branched-chain ketoacid dehydrogenase, glutamate dehydrogenase, glutamic acid decarboxylase, field excitatory postsynaptic potentials, concussion
- MeSH terms
- Amino Acids, Branched-Chain, Animals, Brain Injuries, Cognition Disorders, Diet, Hippocampus, Humans, Male, Mice, Inbred C57BL, Synaptic Transmission, Glutamic Acid, Mice
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