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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bjorndahl, Trent Han, Beomsoo Kumar, Praveen K. Sherman, Eric Mann, David Wishart, David Yilmaz, Ali Bahado-singh, Ray O. Green, Brian D. Graham, Stewart F. |
| Description | Author Affiliation: Graham SF ( Beaumont Research Institute, Beaumont Health, 3811 W. 13 Mile Road, Royal Oak, MI 48073, United States. Electronic address: stewart.graham@beaumont.edu.); Kumar PK ( Beaumont Research Institute, Beaumont Health, 3811 W. 13 Mile Road, Royal Oak, MI 48073, United States.); Bjorndahl T ( Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada); Han B ( Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada); Yilmaz A ( Beaumont Research Institute, Beaumont Health, 3811 W. 13 Mile Road, Royal Oak, MI 48073, United States.); Sherman E ( University of Michigan, Ann Arbour, MI, United States.); Bahado-Singh RO ( Beaumont Research Institute, Beaumont Health, 3811 W. 13 Mile Road, Royal Oak, MI 48073, United States.); Wishart D ( Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada); Mann D ( Institute of Brain Behavior and Mental Health, University of Manchester, UK.); Green BD ( Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Stranmillis Road, Belfast BT9 5AG, UK.) |
| Abstract | Huntington's disease (HD) is an autosomal neurodegenerative disorder affecting approximately 5–10 persons per 100,000 worldwide. The pathophysiology of HD is not fully understood but the age of onset is known to be highly dependent on the number of CAG triplet repeats in the huntingtin gene. Using $^{1}$ H NMR spectroscopy this study biochemically profiled 39 brain metabolites in post-mortem striatum (n = 14) and frontal lobe (n = 14) from HD sufferers and controls (n = 28). Striatum metabolites were more perturbed with 15 significantly affected in HD cases, compared with only 4 in frontal lobe (p < 0.05; q < 0.3). The metabolite which changed most overall was urea which decreased 3.25-fold in striatum (p < 0.01). Four metabolites were consistently affected in both brain regions. These included the neurotransmitter precursors tyrosine and l -phenylalanine which were significantly depleted by 1.55–1.58-fold and 1.48–1.54-fold in striatum and frontal lobe, respectively (p = 0.02–0.03). They also included l -leucine which was reduced 1.54–1.69-fold (p = 0.04–0.09) and myo-inositol which was increased 1.26–1.37-fold (p < 0.01). Logistic regression analyses performed with MetaboAnalyst demonstrated that data obtained from striatum produced models which were profoundly more sensitive and specific than those produced from frontal lobe. The brain metabolite changes uncovered in this first $^{1}$ H NMR investigation of human HD offer new insights into the disease pathophysiology. Further investigations of striatal metabolite disturbances are clearly warranted. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 9 |
| Volume Number | 1862 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2016-09-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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