Chronic desipramine treatment rescues depression-related, social and cognitive deficits in Engrailed-2 knockout mice

J. Brielmaier, J. M. Senerth, Jill L Silverman, P. G. Matteson, J. H. Millonig, E. Dicicco-Bloom, Jacqueline Crawley

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Engrailed-2 (En2) is a homeobox transcription factor that regulates neurodevelopmental processes including neuronal connectivity and elaboration of monoaminergic neurons in the ventral hindbrain. We previously reported abnormalities in brain noradrenergic concentrations in En2 null mutant mice that were accompanied by increased immobility in the forced swim test, relevant to depression. An EN2 genetic polymorphism has been associated with autism spectrum disorders, and mice with a deletion in En2 display social abnormalities and cognitive deficits that may be relevant to multiple neuropsychiatric conditions. This study evaluated the ability of chronic treatment with desipramine (DMI), a selective norepinephrine (NE) reuptake inhibitor and classical antidepressant, to reverse behavioral abnormalities in En2-/- mice. Desipramine treatment significantly reduced immobility in the tail suspension and forced swim tests, restored sociability in the three-chambered social approach task and reversed impairments in contextual fear conditioning in En2-/- mice. Our findings indicate that modulation of brain noradrenergic systems rescues the depression-related phenotype in En2-/- mice and suggest new roles for NE in the pathophysiology of the social and cognitive deficits seen in neuropsychiatric disorders such as autism or schizophrenia.

Original languageEnglish (US)
Pages (from-to)286-298
Number of pages13
JournalGenes, Brain and Behavior
Volume13
Issue number3
DOIs
StatePublished - Mar 2014

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Keywords

  • Autism
  • Depression
  • Desipramine
  • Knockout mouse
  • Norepinephrine
  • Social behavior

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

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