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Dietary branched chain amino acids ameliorate injury-induced cognitive impairment

Jeffrey T. Cole, Christina M. Mitala, Suhali Kundu, Ajay Verma, Jaclynn A. Elkind, Itzhak Nissim, and Akiva S. Cohen
PNAS January 5, 2010 107 (1) 366-371; https://doi.org/10.1073/pnas.0910280107
Jeffrey T. Cole
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Christina M. Mitala
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Suhali Kundu
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Ajay Verma
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Jaclynn A. Elkind
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Itzhak Nissim
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Akiva S. Cohen
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  1. Edited by Richard L. Huganir, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved November 6, 2009 (received for review September 11, 2009)

This article has a correction. Please see:

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Abstract

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.

  • branched chain amino acids
  • cognitive impairment
  • hippocampus
  • tramautic brain injury

Footnotes

  • 2To whom correspondence should be addressed. E-mail: cohena{at}email.chop.edu
  • Author contributions: J.T.C., A.V., and A.S.C. designed research; J.T.C., C.M.M., S.K., J.A.E., and I.N. performed research; J.T.C. and A.S.C. analyzed data; and J.T.C., and A.S.C. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/cgi/content/full/0910280107/DCSupplemental.

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Dietary branched chain amino acids ameliorate injury-induced cognitive impairment
Jeffrey T. Cole, Christina M. Mitala, Suhali Kundu, Ajay Verma, Jaclynn A. Elkind, Itzhak Nissim, Akiva S. Cohen
Proceedings of the National Academy of Sciences Jan 2010, 107 (1) 366-371; DOI: 10.1073/pnas.0910280107

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Dietary branched chain amino acids ameliorate injury-induced cognitive impairment
Jeffrey T. Cole, Christina M. Mitala, Suhali Kundu, Ajay Verma, Jaclynn A. Elkind, Itzhak Nissim, Akiva S. Cohen
Proceedings of the National Academy of Sciences Jan 2010, 107 (1) 366-371; DOI: 10.1073/pnas.0910280107
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