BDNF+/- rats exhibit depressive phenotype and altered expression of genes relevant in mood disorders

Lena-Sophie Martis, Ove Wiborg, Megan C Holmes, Anjanette P Harris

Research output: Contribution to journalJournal articleResearchpeer-review

14 Citations (Scopus)
155 Downloads (Pure)

Abstract

Major depressive disorder (MDD) is a leading contributor to the global burden of disease. However, the causal relationship of risk factors, such as genetic predisposition or experience of augmented stress, remain unknown. Numerous studies in humans and rodents have implicated brain-derived neurotrophic factor (BDNF) in MDD pathology, as a genetic risk factor and a factor regulated by stress. Until now, the majority of preclinical studies have employed genetically modified mice as their model of choice. However, mice display a limited behavioural repertoire and lack expression of circulating BDNF, which is present in rats and humans. Therefore, heterozygous BDNF (BDNF+/- ) rats were tested for affective behaviours and accompanying expression of key genes associated with affective disorders in the brain. We found that BDNF+/- rats, which have reduced BDNF levels in brain and plasma, displayed symptoms of anhedonia, a core symptom of MDD, and anxiety-like behaviour, but no behavioural despair or cognitive impairments. This was accompanied by changes in the expression of genes that are implicated in modulation of the stress response and affective disorders. Hence, glucocorticoid receptor, neuregulin 1 and disrupted-in-schizophrenia 1 gene expression were upregulated in the prefrontal cortex of BDFN+/- rats, whereas FK506 binding protein 5 levels were decreased in the hippocampus. We conclude that a reduction in BDNF levels alters expression of genes associated with affective disorders, which may contribute to the development of depressive-like symptoms.

Original languageEnglish
Article numbere12546
JournalGenes, Brain and Behavior
Volume18
Issue number2
Pages (from-to)e12546
Number of pages11
ISSN1601-1848
DOIs
Publication statusPublished - Feb 2019

Keywords

  • Animals
  • Brain/metabolism
  • Brain-Derived Neurotrophic Factor/genetics
  • Depressive Disorder, Major/genetics
  • Female
  • Heterozygote
  • Male
  • Nerve Tissue Proteins/genetics
  • Neuregulin-1/genetics
  • Phenotype
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid/genetics
  • Tacrolimus Binding Proteins/genetics
  • hippocampus
  • prefrontal cortex
  • transgenic rats
  • GR
  • Nrg1
  • Fkbp5
  • anxiety
  • Disc1
  • anhedonia
  • brain-derived neurotrophic factor

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