PMID- 12809693
OWN - NLM
STAT- MEDLINE
DCOM- 20030912
LR  - 20190712
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 119
IP  - 3
DP  - 2003
TI  - The influence of specific noradrenergic and serotonergic lesions on the 
      expression of hippocampal brain-derived neurotrophic factor transcripts following 
      voluntary physical activity.
PG  - 721-32
AB  - Previous studies have shown that hippocampal brain-derived neurotrophic factor 
      (BDNF) mRNA levels are significantly increased in rats allowed free access to 
      exercise wheels and/or administered antidepressant medications. Enhancement of 
      BDNF may be crucial for the clinical effect of antidepressant interventions. 
      Since increased function of the noradrenergic and/or serotonergic systems is 
      thought to be an important initial mechanism of antidepressant medications, we 
      sought to test the hypothesis that noradrenergic or serotonergic function is 
      essential for the increased BDNF transcription occurring with exercise. In 
      addition, individual transcript variants of BDNF were examined, as evidence 
      exists they are differentially regulated by discrete interventions, and are 
      expressed in distinct sub-regions of the hippocampus. The neurotransmitter 
      system-specific neurotoxins p-chloroamphetamine (serotonergic) and 
      N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (noradrenergic) were administered to 
      rats prior to commencing voluntary wheel-running activity. In situ hybridization 
      experiments revealed an absence of exercise-induced full-length BDNF mRNA 
      elevations in the hippocampi of noradrenergic-lesioned rats. In addition, the 
      striking elevation of the exon I transcript in the dentate gyrus was removed with 
      this noradrenergic lesion. In contrast, other transcript variants (exons II and 
      III) were elevated in several hippocampal regions as a result of this lesion. In 
      serotonin-lesioned rats, the significant increases in full-length BDNF, exon I 
      and exon II mRNA levels were sustained without alteration (with the exception of 
      exon IV in the cornus ammonis subregion 4, CA4). Overall, these results indicate 
      that an intact noradrenergic system may be crucial for the observed ability of 
      exercise to enhance full-length and exon I hippocampal BDNF mRNA expression. In 
      addition, these results suggest that the promoter linked to exon I may provide a 
      major regulatory point for BDNF mRNA expression in the dentate gyrus. Elevations 
      of other exons, such as II and III, may require the activation of separate 
      neurotransmitter systems and intracellular pathways.
FAU - Garcia, C
AU  - Garcia C
AD  - Department of Biological Sciences, California State University, 5151 State 
      University Drive, 90032, Los Angeles, CA, USA.
FAU - Chen, M J
AU  - Chen MJ
FAU - Garza, A A
AU  - Garza AA
FAU - Cotman, C W
AU  - Cotman CW
FAU - Russo-Neustadt, A
AU  - Russo-Neustadt A
LA  - eng
GR  - MH59776/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Antidepressive Agents)
RN  - 0 (Benzylamines)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neurotoxins)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 333DO1RDJY (Serotonin)
RN  - 64-12-0 (p-Chloroamphetamine)
RN  - PQ1P7JP5C1 (DSP 4)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Alternative Splicing/drug effects/genetics
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Benzylamines/pharmacology
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/*genetics
MH  - Denervation
MH  - Depressive Disorder/*drug therapy/metabolism/physiopathology
MH  - Exons/genetics
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Hippocampus/drug effects/*metabolism/physiopathology
MH  - Immunohistochemistry
MH  - Male
MH  - Neurons/drug effects/metabolism
MH  - Neurotoxins/pharmacology
MH  - Norepinephrine/*deficiency
MH  - Physical Conditioning, Animal/*physiology
MH  - Protein Isoforms/drug effects/genetics
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*deficiency
MH  - Transcription, Genetic/drug effects/genetics
MH  - Up-Regulation/drug effects/*physiology
MH  - p-Chloroamphetamine/pharmacology
EDAT- 2003/06/18 05:00
MHDA- 2003/09/13 05:00
CRDT- 2003/06/18 05:00
PHST- 2003/06/18 05:00 [pubmed]
PHST- 2003/09/13 05:00 [medline]
PHST- 2003/06/18 05:00 [entrez]
AID - S0306452203001921 [pii]
AID - 10.1016/s0306-4522(03)00192-1 [doi]
PST - ppublish
SO  - Neuroscience. 2003;119(3):721-32. doi: 10.1016/s0306-4522(03)00192-1.