Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain
Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain
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DOI：
10.1016/s0006-3223(03)00073-8
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发表时间：
2003-10-01
影响因子：
10.6
通讯作者：
Madsen, TM
中科院分区：
文献类型：
--
作者：
Altar, CA;Whitehead, RE;Madsen, TM
背景：脑源性神经营养因子在脑内的抗抑郁作用，以及脑源性神经营养因子mRNA及其受体在电惊厥(ECS)和抗抑郁药物中的上调，提示BDNF蛋白的增加可能起到了作用。方法：我们用两点酶联免疫吸附试验(EL ISA)检测了每天接受ECS或每天注射抗抑郁药物的成年雄性大鼠6个脑区的BDNF蛋白水平。结果：BDNF ELISA法验证了BDNF蛋白在+/BDNF基因敲除小鼠脑内50%的丢失，重组BDNF蛋白的回收率为60%-100%并通过在六个脑区测量的脑源性神经营养因子的数量和区域变化。连续10天暴露于ECS可增加顶叶皮质(219%)、内嗅皮质(153%)、海马区(132%)、额叶皮质(94%)、新纹状体(67%)和隔区(29%)的BDNF蛋白。脑源性神经营养因子在海马区和额叶皮质中逐渐增加，第4天达到高峰。上升在最后一次ECS后15小时达到顶峰，此后至少持续3天。每日注射单胺(MAO)-A和-B抑制剂三羟环丙胺(8-10 mg/kg，ip)2周可使额叶皮质BDNF增加15%，治疗3周可使额叶皮质增加18%，新纹状体增加29%。三羟环丙胺、氟西汀和去甲基米帕明不增加脑组织BDNF的表达。结论：脑内BDNF蛋白的升高与ECS和MAO抑制剂对耐药的重度抑郁障碍有较好的治疗效果一致，并可能预示更有效的干预措施的抗抑郁作用。(C)2003年生物精神病学学会。
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. (C) 2003 Society of Biological Psychiatry.