GC-MS metabolomic analysis reveals significant alterations in cerebellar metabolic physiology in a mouse model of adult onset hypothyroidism

Constantinou, Caterina, Chrysanthopoulos, Panagiotis K., Margarity, Marigoula and Klapa, Maria I. (2011) GC-MS metabolomic analysis reveals significant alterations in cerebellar metabolic physiology in a mouse model of adult onset hypothyroidism. Journal of Proteome Research, 10 2: 869-879. doi:10.1021/pr100699m


Author Constantinou, Caterina
Chrysanthopoulos, Panagiotis K.
Margarity, Marigoula
Klapa, Maria I.
Title GC-MS metabolomic analysis reveals significant alterations in cerebellar metabolic physiology in a mouse model of adult onset hypothyroidism
Journal name Journal of Proteome Research   Check publisher's open access policy
ISSN 1535-3893
1535-3907
Publication date 2011-02-04
Year available 2010
Sub-type Article (original research)
DOI 10.1021/pr100699m
Open Access Status
Volume 10
Issue 2
Start page 869
End page 879
Total pages 11
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Subject 1600 Chemistry
Formatted abstract
Although adult-onset hypothyroidism (AOH) has been connected to neural activity alterations, including movement, behavioral, and mental dysfunctions, the underlying changes in brain metabolic physiology have not been investigated in a systemic and systematic way. The current knowledge remains fragmented, referring to different experimental setups and recovered from various brain regions. In this study, we developed and applied a gas chromatography-mass spectrometry (GC-MS) metabolomics protocol to obtain a holistic view of the cerebellar metabolic physiology in a Balb/cJ mouse model of prolonged adult-onset hypothyroidism induced by a 64-day treatment with 1% potassium perchlorate in the drinking water of the animals. The high-throughput analysis enabled the correlation between multiple paralleloccurring metabolic phenomena; some have been previously related to AOH, while others implicated new pathways, designating new directions for further research. Specifically, an overall decline in the metabolic activity of the hypothyroid compared to the euthyroid cerebellum was observed, characteristically manifested in energy metabolism, glutamate/glutamine metabolism, osmolytic/antioxidant capacity, and protein/lipid synthesis. These alterations provide strong evidence that the mammalian cerebellum is metabolically responsive to AOH. In light of the cerebellum core functions and its increasingly recognized role in neurocognition, these findings further support the known phenotypic manifestations of AOH into movement and cognitive dysfunctions.
Keyword High-throughput biomolecular analysis
Adult brain energy metabolism
Thyroid hormone actions on adult brain
Potassium perchlorate
Mouse model
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Australian Institute for Bioengineering and Nanotechnology Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 27 Nov 2013, 19:44:42 EST by System User on behalf of Aust Institute for Bioengineering & Nanotechnology