Combining small-volume metabolomic and transcriptomic approaches for assessing brain chemistry

Ann M. Knolhoff, Katherine M. Nautiyal, Peter Nemes, Sergey Kalachikov, Irina Morozova, Rae Silver, Jonathan V. Sweedler

Research output: Contribution to journalArticle

Abstract

The integration of disparate data types provides a more complete picture of complex biological systems. Here we combine small-volume metabolomic and transcriptomic platforms to determine subtle chemical changes and to link metabolites and genes to biochemical pathways. Capillary electrophoresis-mass spectrometry (CE-MS) and whole-genome gene expression arrays, aided by integrative pathway analysis, were utilized to survey metabolomic/transcriptomic hippocampal neurochemistry. We measured changes in individual hippocampi from the mast cell mutant mouse strain, C57BL/6 KitW-sh/W-sh. These mice have a naturally occurring mutation in the white spotting locus that causes reduced c-Kit receptor expression and an inability of mast cells to differentiate from their hematopoietic progenitors. Compared with their littermates, the mast cell-deficient mice have profound deficits in spatial learning, memory, and neurogenesis. A total of 18 distinct metabolites were identified in the hippocampus that discriminated between the C57BL/6 Kit W-sh/W-sh and control mice. The combined analysis of metabolite and gene expression changes revealed a number of altered pathways. Importantly, results from both platforms indicated that multiple pathways are impacted, including amino acid metabolism, increasing the confidence in each approach. Because the CE-MS and expression profiling are both amenable to small-volume analysis, this integrated analysis is applicable to a range of volume-limited biological systems.

Original languageEnglish (US)
Pages (from-to)3136-3143
Number of pages8
JournalAnalytical chemistry
Volume85
Issue number6
DOIs
StatePublished - Mar 19 2013

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ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Knolhoff, A. M., Nautiyal, K. M., Nemes, P., Kalachikov, S., Morozova, I., Silver, R., & Sweedler, J. V. (2013). Combining small-volume metabolomic and transcriptomic approaches for assessing brain chemistry. Analytical chemistry, 85(6), 3136-3143. https://doi.org/10.1021/ac3032959