Peripheral BDNF Produces Antidepressant-Like Effects in Cellular and Behavioral Models
Contact Information
Keywords
Ronald S. Duman, ronald.duman@yale.edu
antidepressant, dentate gyrus, neurogenesis, depression, neurotrophic factor, serum
Abstract
Recent clinical studies demonstrate that serum levels of brain-derived neurotrophic factor (BDNF) are significantly decreased in patients with major depressive disorder (MDD) and that antidepressant treatments reverse this effect, indicating that serum BDNF is a biomarker of MDD. These findings raise the possibility that serum BDNF may also have effects on neuronal activity and behavior, but the functional significance of altered serum BDNF is unknown. To address this issue, we determined the influence of peripheral BDNF administration on depression- and anxiety-like behavior, including the forced swim test (FST), chronic unpredictable stress (CUS)/anhedonia, novelty-induced hypophagia (NIH) test, and elevated-plus maze (EPM). Furthermore, we examined adult hippocampal neurogenesis as well as hippocampal and striatal expression of BDNF, extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), in order to determine whether peripherally administered BDNF produces antidepressant-like cellular responses in the brain. Peripheral BDNF administration increased mobility in the FST, attenuated the effects of CUS on sucrose consumption, decreased latency in the NIH test, and increased time spent in the open arms of an EPM. Moreover, adult hippocampal neurogenesis was increased after chronic, peripheral BDNF administration. We also found that BDNF levels as well as expression of pCREB and pERK were elevated in the hippocampus of adult mice receiving peripheral BDNF. Taken together, these results indicate that peripheral/serum BDNF may not only represent a biomarker of MDD, but also have functional consequences on molecular signaling substrates, neurogenesis, and behavior.
Citation
Schmidt, H. D., & Duman, R. S. (2010). Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 35(12), 2378–2391. https://doi.org/10.1038/npp.2010.114
DOI
10.1038/npp.2010.114
EWB Constructs:
homeostasis
EWB Measures:
elevated plus maze, open field test
data availability:
No
data availability details:
N/A
brain imaging paradigm:
hippocampus-dentate gyrus and PFC
brain region/circuit:
Exclusion Criteria:
N/A
Inclusion Criteria
N/A
Non-EWB Behavioral
Measures:
forced swim test, novelty induced hyphagia, chronic stress
First author:
Heath D Schmidt
species:
mouse
sample size:
62
study design:
case control
longitudinal data?
No
younger controls?
N/A
interventions:
Administered BDNF to mice and examined anxiety-like and depressive-like behaviors and cellular responses
study population:
N/A
sex (% female):
0%
ethnicity (%white)
N/A
Age (mean, sd):
8-10 weeks
biological/Physiological Measures:
N/A