Molecular and Functional Sex Differences of Noradrenergic Neurons in the Mouse Locus Coeruleus

Bernard Mulvey, Dionnet L. Bhatti, Sandeep Gyawali, Allison M. Lake, Skirmantas Kriaucionis, Christopher P. Ford, Michael R. Bruchas, Nathaniel Heintz, Joseph D. Dougherty

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Preclinical work has long focused on male animals, though biological sex clearly influences risk for certain diseases, including many psychiatric disorders. Such disorders are often treated by drugs targeting the CNS norepinephrine system. Despite roles for noradrenergic neurons in behavior and neuropsychiatric disease models, their molecular characterization has lagged. We profiled mouse noradrenergic neurons in vivo, defining over 3,000 high-confidence transcripts expressed therein, including druggable receptors. We uncovered remarkable sex differences in gene expression, including elevated expression of the EP3 receptor in females—which we leverage to illustrate the behavioral and pharmacologic relevance of these findings—and of Slc6a15 and Lin28b, both major depressive disorder (MDD)-associated genes. Broadly, we present a means of transcriptionally profiling locus coeruleus under baseline and experimental conditions. Our findings underscore the need for preclinical work to include both sexes and suggest that sex differences in noradrenergic neurons may underlie behavioral differences relevant to disease. Mulvey et al. present gene expression data from adult mouse norepinephrine neurons of the locus coeruleus (LC). They discover that over 100 genes are sex-differentially expressed in LC, including receptors, and that these receptor expression differences are substantial enough to have sex-specific consequences for LC neurons and the behaviors they control.

Original languageEnglish
Pages (from-to)2225-2235
Number of pages11
JournalCell Reports
Volume23
Issue number8
DOIs
StatePublished - May 22 2018

Keywords

  • gene expression
  • locus coeruleus
  • norepinephrine
  • open-field task
  • sex differences
  • sexual dimorphism

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