Effects of antidepressant treatment on mice lacking brain-derived neurotrophic factor expression through promoter IV

Kazuko Sakata, Joshua R. Mastin, Sean M. Duke, Meghan G. Vail, Abigail E. Overacre, Brittany E. Dong, Shanker Jha

Research output: Contribution to journalArticle

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Abstract

Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depression; mice lacking BDNF expression through promoter IV (BDNF-KIV) exhibit a depression-like phenotype. We tested our hypothesis that deficits caused by promoter IV deficiency (depression-like behavior, decreased levels of BDNF, and neurogenesis in the hippocampus) could be rescued by a 3-week treatment with different types of antidepressants: fluoxetine, phenelzine, duloxetine, or imipramine. Each antidepressant reduced immobility time in the tail suspension test without affecting locomotor activity in the open field test in both BDNF-KIV and control wild type mice, except that phenelzine increased locomotor activity in wild type mice and anxiety-like behavior in BDNF-KIV mice. The antidepressant treatments were insufficient to reverse decreased BDNF levels caused by promoter IV deficiency. No antidepressant treatment increased the hippocampal progenitors of either genotype, whereas phenelzine decreased the surviving progenitors in both genotypes. The antidepressant treatments differently affected the dendritic extension of hippocampal immature neurons: fluoxetine and imipramine increased extension in both genotypes, duloxetine increased it only in BDNF-KIV mice, and phenelzine decreased it only in wild type mice. Interestingly, a saline-only injection increased neurogenesis and dendrite extensions in both genotypes. Our results indicate that the behavioral effects in the tail suspension test by antidepressants do not require promoter IV-driven BDNF expression and occur without a detectable increase in hippocampal BDNF levels and neurogenesis but may involve increased dendritic reorganisation of immature neurons. In conclusion, the antidepressant treatment demonstrated limited efficacy; it partially reversed the defective phenotypes caused by promoter IV deficiency but not hippocampal BDNF levels.

Original languageEnglish (US)
Pages (from-to)1863-1874
Number of pages12
JournalEuropean Journal of Neuroscience
Volume37
Issue number11
DOIs
StatePublished - Jun 1 2013

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Brain-Derived Neurotrophic Factor
Antidepressive Agents
Phenelzine
Neurogenesis
Genotype
Therapeutics
Hindlimb Suspension
Imipramine
Fluoxetine
Locomotion
Depression
Phenotype
Neurons
Dendrites
Hippocampus
Anxiety

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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Effects of antidepressant treatment on mice lacking brain-derived neurotrophic factor expression through promoter IV. / Sakata, Kazuko; Mastin, Joshua R.; Duke, Sean M.; Vail, Meghan G.; Overacre, Abigail E.; Dong, Brittany E.; Jha, Shanker.

In: European Journal of Neuroscience, Vol. 37, No. 11, 01.06.2013, p. 1863-1874.

Research output: Contribution to journalArticle

Sakata, Kazuko ; Mastin, Joshua R. ; Duke, Sean M. ; Vail, Meghan G. ; Overacre, Abigail E. ; Dong, Brittany E. ; Jha, Shanker. / Effects of antidepressant treatment on mice lacking brain-derived neurotrophic factor expression through promoter IV. In: European Journal of Neuroscience. 2013 ; Vol. 37, No. 11. pp. 1863-1874.
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