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 in their action. Methods. BDNF protein levels were measured with a 2-site ELISA in 6 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 6 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 the septum (29%) compared to control animals that received sham ECS. BDNF increased gradually in the hippocampus and frontal cortex, with a peak response by the fourth day of ECS treatment. These increases peaked at 15 hr after the last ECS and lasted at least 3 days thereafter. Four Two weeks of daily injections with the MAO-A and -B inhibitor tranylcypromine (8-10 mg/kg, i.p.) failed to alter hippocampal BDNF, whereas 2 weeks of treatment elevatedincreased BDNF by 15% in the frontal cortex and 3 weeks treatment elevated increased it BDNF by 18% in the frontal cortex and by 29% in the neostriatum. Neither tranylcypromine, fluoxetine, nor desmethylimipramine elevated 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 mediate be predictive for the antidepressant action of these the more highly efficacious interventions.
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