PMID- 23564488
OWN - NLM
STAT- MEDLINE
DCOM- 20140212
LR  - 20211021
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 48
IP  - 1
DP  - 2013 Aug
TI  - Lack of serotonin transporter alters BDNF expression in the rat brain during 
      early postnatal development.
PG  - 244-56
LID - 10.1007/s12035-013-8449-z [doi]
AB  - It is well established that alterations of the serotoninergic system may 
      contribute to the pathophysiology of mood disorders. Accordingly, it has been 
      demonstrated that genetic deletion of the serotonin transporter (SERT) in rodents 
      leads to an anxious and depressive phenotype, which is also associated with 
      reduced neuronal plasticity. Indeed, we have demonstrated that adult SERT(-/-) 
      animals show decreased brain-derived neurotrophic factor (BDNF) expression, as 
      well as reduced levels of transcription factor regulating the neurotrophin 
      transcription. While these changes may represent long-term consequences of 
      impaired function of the transporter during development, no information exists 
      with respect to the developmental profile of such changes. Using SERT(-/-) rats 
      at different ages, we found that the impairment in neuroplasticity originates 
      early in development and worsens during the first 3 weeks of life. Indeed, we 
      observed that BDNF expression was reduced at birth and that the magnitude of 
      these changes became more pronounced starting from PND21, being sustained by 
      epigenetic mechanisms as well as alterations in the expression of specific 
      transcription factors, including Npas4 and CaRF. These results suggest that an 
      impairment of SERT may affect BDNF expression throughout postnatal development. 
      These early changes may increase stress susceptibility during critical windows of 
      brain maturation, which may eventually lead to the heightened predisposition to 
      mood disorders found in individual carrying genetic variants of the serotonin 
      transporter.
FAU - Calabrese, Francesca
AU  - Calabrese F
AD  - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita' degli Studi 
      di Milano, Milan, Italy.
FAU - Guidotti, Gianluigi
AU  - Guidotti G
FAU - Middelman, Anthonieke
AU  - Middelman A
FAU - Racagni, Giorgio
AU  - Racagni G
FAU - Homberg, Judith
AU  - Homberg J
FAU - Riva, Marco A
AU  - Riva MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130409
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Gadd45b protein, rat)
RN  - 0 (Npas4 protein, rat)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, rat)
RN  - 0 (Transcription Factors)
RN  - 0 (calcium response transcription factor 1, rat)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Antigens, Differentiation/genetics/metabolism
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
MH  - Brain/*growth & development/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/genetics/metabolism
MH  - DNA (Cytosine-5-)-Methyltransferase 1
MH  - DNA (Cytosine-5-)-Methyltransferases/genetics/metabolism
MH  - DNA Methylation/genetics
MH  - Exons/genetics
MH  - *Gene Expression Regulation, Developmental
MH  - Hippocampus/growth & development/metabolism
MH  - Male
MH  - Prefrontal Cortex/growth & development/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Isoforms/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin Plasma Membrane Transport Proteins/deficiency/*metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - gamma-Aminobutyric Acid/metabolism
EDAT- 2013/04/09 06:00
MHDA- 2014/02/13 06:00
CRDT- 2013/04/09 06:00
PHST- 2012/12/10 00:00 [received]
PHST- 2013/03/25 00:00 [accepted]
PHST- 2013/04/09 06:00 [entrez]
PHST- 2013/04/09 06:00 [pubmed]
PHST- 2014/02/13 06:00 [medline]
AID - 10.1007/s12035-013-8449-z [doi]
PST - ppublish
SO  - Mol Neurobiol. 2013 Aug;48(1):244-56. doi: 10.1007/s12035-013-8449-z. Epub 2013 
      Apr 9.