Data from: Genetic or toxicant-induced disruption of vesicular monoamine storage and global metabolic profiling in Caenorhabditis elegans

The proper storage and release of monoamines contributes to a wide range
of neuronal activity. Here, we examine the effects of altered vesicular
monoamine transport in the nematode C. elegans. The gene cat-1 is
responsible for the encoding of the vesicular monoamine transporter (VMAT)
in C. elegans and is analogous to the mammalian vesicular monoamine
transporter 2 (VMAT2). Our laboratory has previously shown that reduced
VMAT2 activity confers vulnerability on catecholamine neurons in mice. The
purpose of this paper was to determine whether this function is conserved
and to determine the impact of reduced VMAT activity in C.
elegans.  Here we show that deletion of cat-1/VMAT increases
sensitivity to the neurotoxicant 1-methyl-4-phenylpyridinium (MPP+) as
measured by enhanced degeneration of dopamine neurons.  Reduced
cat-1/VMAT also induces changes in dopamine-mediated behaviors.
High-resolution mass spectrometry-based metabolomics in the whole organism
reveals changes in amino acid metabolism, including tyrosine metabolism in
the cat-1/VMAT mutants. Treatment with MPP+ disrupted tryptophan
metabolism. Both conditions altered glycerophospholipid metabolism,
suggesting a convergent pathway of neuronal dysfunction.  Our
results demonstrate the evolutionarily conserved nature of monoamine
function in C. elegans and further suggest that HRMS-based metabolomics
can be used in this model to study environmental and genetic contributors
to complex human disease.