Abstract
Background
The antidepressant-like effects of brain-derived neurotrophic factor (BDNF) infusions
in brain, and the upregulation of BDNF mRNA and its receptor in rats exposed to electroconvulsive
seizure (ECS) and antidepressants, suggested a role for increased BDNF protein.
Methods
We measured BDNF protein levels with a two-site enzyme-linked immunosorbent assay
(ELISA) in six brain regions of adult male rats that received daily ECS or daily injections
of antidepressant drugs.
Results
The BDNF ELISA method was validated by the 50% loss of BDNF protein in the brains
of +/− BDNF knockout mice, the 60%–100% recovery of spiked recombinant BDNF, and by
the amounts and regional variations of BDNF measured in the six brain regions. Ten
consecutive daily exposures to ECS increased BDNF protein in the parietal cortex (219%),
entorhinal cortex (153%), hippocampus (132%), frontal cortex (94%), neostriatum (67%),
and septum (29%). BDNF increased gradually in the hippocampus and frontal cortex,
with a peak response by the fourth day of ECS. Increases peaked at 15 hours after
the last ECS and lasted at least 3 days thereafter. Two weeks of daily injections
with the monoamine (MAO)-A and -B inhibitor tranylcypromine (8–10 mg/kg, IP) increased
BDNF by 15% in the frontal cortex, and 3 weeks treatment increased it by 18% in the
frontal cortex and by 29% in the neostriatum. Tranylcypromine, fluoxetine, and desmethylimipramine
did not elevate BDNF in the hippocampus.
Conclusions
Elevations in BDNF protein in brain are consistent with the greater treatment efficacy
of ECS and MAO inhibitors in drug-resistant major depressive disorder and may be predictive
for the antidepressant action of the more highly efficacious interventions.
Keywords
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Article info
Publication history
Accepted:
January 13,
2003
Received in revised form:
December 30,
2002
Received:
September 23,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
