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

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 parallel-occurring 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.
AuthorsCaterina Constantinou, Panagiotis K Chrysanthopoulos, Marigoula Margarity, Maria I Klapa
JournalJournal of proteome research (J Proteome Res) Vol. 10 Issue 2 Pg. 869-79 (Feb 04 2011) ISSN: 1535-3907 [Electronic] United States
PMID21028881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Perchlorates
  • Potassium Compounds
  • potassium perchlorate
Topics
  • Animals
  • Body Weight
  • Cerebellum (chemistry, metabolism)
  • Cluster Analysis
  • Disease Models, Animal
  • Gas Chromatography-Mass Spectrometry (methods)
  • Hypothyroidism (chemically induced, metabolism)
  • Male
  • Metabolic Networks and Pathways
  • Metabolome
  • Metabolomics (methods)
  • Mice
  • Mice, Inbred BALB C
  • Microarray Analysis
  • Perchlorates
  • Potassium Compounds
  • Principal Component Analysis
  • Reproducibility of Results

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