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 KitW-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.