PMID- 30294251
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 12
DP  - 2018
TI  - Selective Depletion of CREB in Serotonergic Neurons Affects the Upregulation of 
      Brain-Derived Neurotrophic Factor Evoked by Chronic Fluoxetine Treatment.
PG  - 637
LID - 10.3389/fnins.2018.00637 [doi]
LID - 637
AB  - Neurotrophic factors are regarded as crucial regulatory components in neuronal 
      plasticity and are postulated to play an important role in depression pathology. 
      The abundant expression of brain-derived neurotrophic factor (BDNF) in various 
      brain structures seems to be of particular interest in this context, as 
      downregulation of BDNF is postulated to be correlated with depression and its 
      upregulation is often observed after chronic treatment with common 
      antidepressants. It is well-known that BDNF expression is regulated by cyclic AMP 
      response element-binding protein (CREB). In our previous study using mice lacking 
      CREB in serotonergic neurons (Creb1(TPH2CreERT2) mice), we showed that selective 
      CREB ablation in these particular neuronal populations is crucial for 
      drug-resistant phenotypes in the tail suspension test observed after fluoxetine 
      administration in Creb1(TPH2CreERT2) mice. The aim of this study was to 
      investigate the molecular changes in the expression of neurotrophins in 
      Creb1(TPH2CreERT2) mice after chronic fluoxetine treatment, restricted to the 
      brain structures implicated in depression pathology with profound serotonergic 
      innervation including the prefrontal cortex (PFC) and hippocampus. Here, we show 
      for the first time that BDNF upregulation observed after fluoxetine in the 
      hippocampus or PFC might be dependent on the transcription factor CREB residing, 
      not within these particular structures targeted by serotonergic projections, but 
      exclusively in serotonergic neurons. This observation may shed new light on the 
      neurotrophic hypothesis of depression, where the effects of BDNF observed after 
      antidepressants in the hippocampus and other brain structures were rather thought 
      to be regulated by CREB residing within the same brain structures. Overall, these 
      results provide further evidence for the pivotal role of CREB in serotonergic 
      neurons in maintaining mechanisms of antidepressant drug action by regulation of 
      BDNF levels.
FAU - Rafa-Zablocka, Katarzyna
AU  - Rafa-Zablocka K
AD  - Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of 
      Sciences, Krakow, Poland.
FAU - Kreiner, Grzegorz
AU  - Kreiner G
AD  - Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of 
      Sciences, Krakow, Poland.
FAU - Baginska, Monika
AU  - Baginska M
AD  - Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of 
      Sciences, Krakow, Poland.
FAU - Nalepa, Irena
AU  - Nalepa I
AD  - Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of 
      Sciences, Krakow, Poland.
LA  - eng
PT  - Journal Article
DEP - 20180920
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC6158386
OTO - NOTNLM
OT  - BDNF
OT  - CREB
OT  - CREM
OT  - NGF
OT  - NTF3
OT  - fluoxetine
OT  - serotonergic system
EDAT- 2018/10/09 06:00
MHDA- 2018/10/09 06:01
PMCR- 2018/01/01
CRDT- 2018/10/09 06:00
PHST- 2018/06/05 00:00 [received]
PHST- 2018/08/24 00:00 [accepted]
PHST- 2018/10/09 06:00 [entrez]
PHST- 2018/10/09 06:00 [pubmed]
PHST- 2018/10/09 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2018.00637 [doi]
PST - epublish
SO  - Front Neurosci. 2018 Sep 20;12:637. doi: 10.3389/fnins.2018.00637. eCollection 
      2018.