title: Combining small-volume metabolomic and transcriptomic approaches for assessing brain chemistry.
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 Kit(W-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.
authors: Department of Chemistry and the Beckman Institute, University of Illinois, Urbana, Illinois 61801, United States.
authors: Ann M
authors: AM
authors: Knolhoff
authors: Katherine M
authors: KM
authors: Nautiyal
authors: Peter
authors: P
authors: Nemes
authors: Sergey
authors: S
authors: Kalachikov
authors: Irina
authors: I
authors: Morozova
authors: Rae
authors: R
authors: Silver
authors: Jonathan V
authors: JV
authors: Sweedler
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic