PMID- 24886632
OWN - NLM
STAT- MEDLINE
DCOM- 20141112
LR  - 20211021
IS  - 1750-1172 (Electronic)
IS  - 1750-1172 (Linking)
VI  - 9
DP  - 2014 May 8
TI  - Brain-blood amino acid correlates following protein restriction in murine maple 
      syrup urine disease.
PG  - 73
LID - 10.1186/1750-1172-9-73 [doi]
AB  - BACKGROUND: Conventional therapy for patients with maple syrup urine disease 
      (MSUD) entails restriction of protein intake to maintain acceptable levels of the 
      branched chain amino acid, leucine (LEU), monitored in blood. However, no data 
      exists on the correlation between brain and blood LEU with protein restriction, 
      and whether correction in blood is reflected in brain. METHODS: To address this 
      question, we fed intermediate MSUD mice diets of 19% (standard) and 6% protein, 
      with collection of sera (SE), striata (STR), cerebellum (CE) and cortex (CTX) for 
      quantitative amino acid analyses. RESULTS: LEU and valine (VAL) levels in all 
      brain regions improved on average 28% when shifting from 19% to 6% protein, 
      whereas the same improvements in SE were on average 60%. Isoleucine (ILE) in 
      brain regions did not improve, while the SE level improved 24% with low-protein 
      consumption. Blood-branched chain amino acids (LEU, ILE, and VAL in sera (SE)) 
      were 362-434 muM, consistent with human values considered within control. 
      Nonetheless, numerous amino acids in brain regions remained abnormal despite 
      protein restriction, including glutamine (GLN), aspartate (ASP), glutamate (GLU), 
      gamma-aminobutyric acid (GABA), asparagine (ASN), citrulline (CIT) and serine 
      (SER). To assess the specificity of these anomalies, we piloted preliminary 
      studies in hyperphenylalaninemic mice, modeling another large neutral 
      aminoacidopathy. Employing an identical dietary regimen, we found remarkably 
      consistent abnormalities in GLN, ASP, and GLU. CONCLUSIONS: Our results suggest 
      that blood amino acid analysis may be a poor surrogate for assessing the outcomes 
      of protein restriction in the large neutral amino acidopathies, and further 
      indicate that chronic neurotransmitter disruptions (GLU, GABA, ASP) may 
      contribute to long-term neurocognitive dysfunction in these disorders.
FAU - Vogel, Kara R
AU  - Vogel KR
FAU - Arning, Erland
AU  - Arning E
FAU - Wasek, Brandi L
AU  - Wasek BL
FAU - McPherson, Sterling
AU  - McPherson S
FAU - Bottiglieri, Teodoro
AU  - Bottiglieri T
FAU - Gibson, K Michael
AU  - Gibson KM
AD  - Experimental and Systems Pharmacology, College of Pharmacy, Washington State 
      University, 412 E, Spokane Falls Blvd,, Pharmaceutical and Biomedical Sciences 
      Building, Room 347, P,O, Box 1495, 99210-1495 Spokane, WA, USA. 
      mike.gibson@wsu.edu.
LA  - eng
GR  - HD58553/HD/NICHD NIH HHS/United States
GR  - NS82286/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140508
PL  - England
TA  - Orphanet J Rare Dis
JT  - Orphanet journal of rare diseases
JID - 101266602
RN  - 0 (Amino Acids)
RN  - 0 (Dietary Proteins)
SB  - IM
MH  - Amino Acids/blood/*metabolism
MH  - Animals
MH  - Brain/*metabolism
MH  - Dietary Proteins/*administration & dosage
MH  - *Disease Models, Animal
MH  - Maple Syrup Urine Disease/*diet therapy/metabolism/physiopathology
MH  - Mice
MH  - Polymerase Chain Reaction
PMC - PMC4022424
EDAT- 2014/06/03 06:00
MHDA- 2014/11/13 06:00
PMCR- 2014/05/08
CRDT- 2014/06/03 06:00
PHST- 2014/02/19 00:00 [received]
PHST- 2014/04/25 00:00 [accepted]
PHST- 2014/06/03 06:00 [entrez]
PHST- 2014/06/03 06:00 [pubmed]
PHST- 2014/11/13 06:00 [medline]
PHST- 2014/05/08 00:00 [pmc-release]
AID - 1750-1172-9-73 [pii]
AID - 10.1186/1750-1172-9-73 [doi]
PST - epublish
SO  - Orphanet J Rare Dis. 2014 May 8;9:73. doi: 10.1186/1750-1172-9-73.