PMID- 24345476
OWN - NLM
STAT- MEDLINE
DCOM- 20140925
LR  - 20140203
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 260
DP  - 2014 Feb 28
TI  - Lack of BDNF expression through promoter IV disturbs expression of monoamine 
      genes in the frontal cortex and hippocampus.
PG  - 265-75
LID - S0306-4522(13)01029-4 [pii]
LID - 10.1016/j.neuroscience.2013.12.013 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of 
      psychiatric conditions including major depression and schizophrenia. Mice lacking 
      activity-driven BDNF expression through promoter IV (knock-in promoter IV: KIV) 
      exhibit depression-like behavior, inflexible learning, and impaired response 
      inhibition. Monoamine systems (serotonin, dopamine, and noradrenaline) are 
      suggested to be involved in depression and schizophrenia since many of the 
      current antidepressants and antipsychotics increase the brain levels of 
      monoamines and/or act on monoamine receptors. To elucidate the impact of 
      activity-driven BDNF on the monoamine systems, we examined mRNA levels for 30 
      monoamine-related genes, including receptors, transporters, and synthesizing 
      enzymes, in KIV and control wild-type mice by using quantitative 
      reverse-transcription polymerase chain reaction (qRT-PCR). mRNA levels were 
      measured in the frontal cortex and hippocampus, which are regions related to 
      depression and schizophrenia and where promoter IV is active. The frontal cortex 
      of KIV mice showed reduced levels of mRNA expression for serotonin receptors 1b, 
      2a, and 5b (5HTR1b, 5HTR2a, 5HTR5b), dopamine D2 receptors (DRD2), and adrenergic 
      receptors alpha 1a and 1d (AdRalpha1a and AdRalpha1b), but increased levels for serotonin 
      synthesizing enzyme, tryptophan hydroxylase (TPH), and dopamine D4 receptor 
      (DRD4) when compared to control wild-type mice. The hippocampus of KIV mice 
      showed decreased levels of 5HTR5b. Our results provide causal evidence that lack 
      of promoter IV-driven BDNF disturbs expression of monoaminergic genes in the 
      frontal cortex and hippocampus. These disturbed expression changes in the 
      monoamine systems may mediate the depression- and schizophrenia-like behavior of 
      KIV mice. Our results also suggest that antidepressant and antipsychotic 
      treatments may actually interfere with and normalize the disturbed monoamine 
      systems caused by reduced activity-dependent BDNF, while the treatment responses 
      to these drugs may differ in the subject with reduced BDNF levels caused by 
      stress and lack of neuronal activity.
CI  - Copyright (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Sakata, K
AU  - Sakata K
AD  - Department of Pharmacology, University of Tennessee Health Science Center, 
      Memphis, TN, USA. Electronic address: ksakata@uthsc.edu.
FAU - Duke, S M
AU  - Duke SM
AD  - Department of Pharmacology, University of Tennessee Health Science Center, 
      Memphis, TN, USA.
LA  - eng
PT  - Journal Article
DEP - 20131215
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Biogenic Monoamines/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Female
MH  - Frontal Lobe/*metabolism
MH  - Hippocampus/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Promoter Regions, Genetic
OTO - NOTNLM
OT  - AdR
OT  - BDNF
OT  - Brain-derived neurotrophic factor
OT  - Ct
OT  - DAT
OT  - DRD2
OT  - DRD4
OT  - EDTA
OT  - EPSC
OT  - FC
OT  - FDR
OT  - HIP
OT  - IPSC
OT  - KIV
OT  - NET
OT  - SE
OT  - SSRI
OT  - TH
OT  - TPH
OT  - WT
OT  - adrenergic receptor
OT  - cycle threshold
OT  - dopamine D2 receptor
OT  - dopamine D4 receptor
OT  - dopamine transporter
OT  - ethylenediaminetetraacetic acid
OT  - excitatory postsynaptic current
OT  - false discovery rate
OT  - frontal cortex
OT  - gene expression
OT  - hippocampus
OT  - inhibitory postsynaptic current
OT  - knock-in promoter IV
OT  - monoamine systems
OT  - norepinephrine transporter
OT  - promoter IV
OT  - qRT-PCR
OT  - quantitative reverse-transcription polymerase chain reaction
OT  - selective serotonin reuptake inhibitor
OT  - standard error of mean
OT  - tryptophan hydroxylase
OT  - tyrosine hydroxylase
OT  - wild-type
EDAT- 2013/12/19 06:00
MHDA- 2014/09/26 06:00
CRDT- 2013/12/19 06:00
PHST- 2013/10/02 00:00 [received]
PHST- 2013/11/29 00:00 [revised]
PHST- 2013/12/06 00:00 [accepted]
PHST- 2013/12/19 06:00 [entrez]
PHST- 2013/12/19 06:00 [pubmed]
PHST- 2014/09/26 06:00 [medline]
AID - S0306-4522(13)01029-4 [pii]
AID - 10.1016/j.neuroscience.2013.12.013 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Feb 28;260:265-75. doi: 10.1016/j.neuroscience.2013.12.013. 
      Epub 2013 Dec 15.