PMID- 16842762
OWN - NLM
STAT- MEDLINE
DCOM- 20061101
LR  - 20171120
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1106
IP  - 1
DP  - 2006 Aug 23
TI  - Biphasic change in BDNF gene expression following antidepressant drug treatment 
      explained by differential transcript regulation.
PG  - 12-20
LID - S0006-8993(06)01576-9 [pii]
LID - 10.1016/j.brainres.2006.05.063 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) has been suggested as a possible target 
      for the treatment of depression. The effect by antidepressant drugs on BDNF mRNA 
      expression is, however, strictly dependent on both treatment duration and time 
      after the last administration. The rat BDNF gene itself is complex and expresses 
      four different mRNA isoforms which can be regulated by different signaling 
      cascades. The aim of the present study was to test the hypothesis that the 
      previously shown biphasic action by the antidepressant drugs on total BDNF 
      expression is explained by differential BDNF transcript regulation. For this 
      purpose, we used in situ hybridization with exon-specific oligo nucleotides for 
      exon V (total BDNF mRNA), exon I (protein synthesis-dependent transcripts), exon 
      III and exon IV (immediate early-gene like-transcripts). Following an acute 
      injection, all three drugs tested: fluoxetine, desipramine and TCP decreased 
      total BDNF mRNA (exon V) as well as exon IV mRNA, while no significant effect was 
      recorded for exons I and III mRNAs. In contrast chronic administration of all 
      three drugs resulted in increased expression of exon V- and exon I-containing 
      transcripts (fluoxetine and TCP only) but no significant changes were recorded 
      for exon III and IV mRNAs. Electroconvulsive shock administration showed 
      up-regulation of all four BDNF mRNAs following a single shock, but after repeated 
      administration increases were restricted to exons I- and V-containing 
      transcripts. In summary, this study shows clear evidence of differential BDNF 
      transcript regulation following acute and chronic antidepressant drug treatment.
FAU - Khundakar, A A
AU  - Khundakar AA
AD  - Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort 
      University, The Gateway, Leicester, LE1 9BH, UK.
FAU - Zetterstrom, T S C
AU  - Zetterstrom TSC
AD  - Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort 
      University, The Gateway, Leicester, LE1 9BH, UK. Electronic address: 
      tscz@dmu.ac.uk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060713
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Antidepressive Agents)
RN  - 0 (Antidepressive Agents, Second-Generation)
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 3E3V44J4Z9 (Tranylcypromine)
RN  - TG537D343B (Desipramine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Antidepressive Agents, Second-Generation/pharmacology
MH  - Antidepressive Agents, Tricyclic/pharmacology
MH  - Brain/*drug effects/metabolism/physiopathology
MH  - Brain Chemistry/*drug effects/genetics
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Depressive Disorder/drug therapy/genetics/metabolism
MH  - Desipramine/pharmacology
MH  - Drug Administration Schedule
MH  - Electroshock
MH  - Exons/drug effects/genetics
MH  - Fluoxetine/pharmacology
MH  - Gene Expression Regulation/*drug effects/physiology
MH  - Male
MH  - Monoamine Oxidase Inhibitors/pharmacology
MH  - RNA, Messenger/*drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Regulatory Elements, Transcriptional/drug effects/genetics
MH  - Transcriptional Activation/drug effects/genetics
MH  - Tranylcypromine/pharmacology
MH  - Up-Regulation/drug effects/genetics
EDAT- 2006/07/18 09:00
MHDA- 2006/11/02 09:00
CRDT- 2006/07/18 09:00
PHST- 2005/09/21 00:00 [received]
PHST- 2006/05/16 00:00 [revised]
PHST- 2006/05/21 00:00 [accepted]
PHST- 2006/07/18 09:00 [pubmed]
PHST- 2006/11/02 09:00 [medline]
PHST- 2006/07/18 09:00 [entrez]
AID - S0006-8993(06)01576-9 [pii]
AID - 10.1016/j.brainres.2006.05.063 [doi]
PST - ppublish
SO  - Brain Res. 2006 Aug 23;1106(1):12-20. doi: 10.1016/j.brainres.2006.05.063. Epub 
      2006 Jul 13.