The (15)N isotope effect as a means for correlating phenotypic alterations and affected pathways in a trait anxiety mouse model.
Stable isotope labeling techniques hold great potential for accurate quantitative proteomics comparisons by MS. To investigate the effect of stable isotopes in vivo, we metabolically labeled high anxiety-related behavior (HAB) mice with the heavy nitrogen isotope (15)N. (15)N-labeled HAB mice exhibited behavioral alterations compared to unlabeled ((14)N) HAB mice in their depression-like phenotype. To correlate behavioral alterations with changes on the molecular level, we explored the (15)N isotope effect on the brain proteome by comparing protein expression levels between (15)N-labeled and (14)N HAB mouse brains using quantitative MS. By implementing two complementary in silico pathway analysis approaches, we were able to identify altered networks in (15)N-labeled HAB mice, including major metabolic pathways such as the tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Here, we discuss the affected pathways with regard to their relevance for the behavioral phenotype and critically assess the utility of exploiting the (15)N isotope effect for correlating phenotypic and molecular alterations.
Department of Proteomics and Biomarkers, Max Planck Institute of Psychiatry, Munich, Germany.
Michaela D
MD
Filiou
Christian
C
Webhofer
Philipp
P
Gormanns
Yaoyang
Y
Zhang
Stefan
S
Reckow
Birgit
B
Bisle
Larysa
L
Teplytska
Elisabeth
E
Frank
Melanie S
MS
Kessler
Giuseppina
G
Maccarrone
Rainer
R
Landgraf
Christoph W
CW
Turck
D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000473:pathology*; D001522:Behavior, Animal; D004195:Disease Models, Animal; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D051379:Mice; D009587:Nitrogen Isotopes; D010641:Phenotype; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D015398:Signal Transduction
D009587:Nitrogen Isotopes; D020543:Proteome