Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV

S. Jha, B. E. Dong, Y. Xue, David Delotterie, M. G. Vail, Kazuko Sakata

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0-2 months), young adult (2-4 months), and old adult (12-14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults.

Original languageEnglish (US)
Article numbere896
JournalTranslational psychiatry
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2016

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Brain-Derived Neurotrophic Factor
Depression
Therapeutics
Young Adult
Hippocampus
Genetic Epigenesis
Hindlimb Suspension
Nerve Growth Factors
Frontal Lobe
Antidepressive Agents

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV. / Jha, S.; Dong, B. E.; Xue, Y.; Delotterie, David; Vail, M. G.; Sakata, Kazuko.

In: Translational psychiatry, Vol. 6, No. 9, e896, 01.09.2016.

Research output: Contribution to journalArticle

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