Selective deletion of leptin receptors in adult hippocampus induces depression-related behaviours

Ming Guo, Tung Yi Huang, Jacob C. Garza, Streamson C. Chua, Xin Yun Lu

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Previous studies have demonstrated that leptin and its receptors (LepRb) in the central nervous system play an important role in regulating depression-and anxiety-related behaviours. However, the physiological functions of LepRb in specific brain regions for mediating different emotional behaviours remain to be defined. In this study, we examined the behavioural effects of LepRb ablation in the adult hippocampus using a series of behavioural paradigms for assessing depression-and anxiety-related behaviours. Targeted deletion of LepRb was achieved using the Cre/loxP site-specific recombination system through bilateral stereotaxic delivery of an adeno-associated virus expressing Cre-recombinase (AAV-Cre) into the dentate gyrus of adult mice homozygous for a floxed leptin receptor allele. AAV-Cre-mediated deletion of the floxed region of LepRb was detected 2 wk after injection. In accordance with this, leptin-stimulated phosphorylation of Akt was attenuated in the hippocampus of AAV-Cre injected mice. Mice injected with AAV-Cre displayed normal locomotor activity and anxiety-like behaviour, as determined in the elevated plus-maze, light-dark box and open field tests, but showed increased depression-like behaviours in the tail suspension, saccharin preference and learned helplessness tests. Taken together, these data suggest that deletion of LepRb in the adult hippocampus is sufficient to induce depression-like behaviours. Our results support the view that leptin signalling in the hippocampus may be essential for positive mood states and active coping to stress.

Original languageEnglish (US)
Pages (from-to)857-867
Number of pages11
JournalInternational Journal of Neuropsychopharmacology
Volume16
Issue number4
DOIs
StatePublished - May 2013

Keywords

  • Anhedonia
  • depression
  • hippocampus
  • learned helplessness
  • leptin receptor LepRb

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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