Takahashi Makoto, Kakita Akiyoshi, Futamura Takashi, Watanabe Yuichiro, Mizuno Makoto, Sakimura Kenji, Castren Eero, Nabeshima Toshitaka, Someya Toshiyuki, Nawa Hiroyuki
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Neurochem. 2006 Nov;99(3):770-80. doi: 10.1111/j.1471-4159.2006.04106.x. Epub 2006 Aug 11.
Brain-derived neurotrophic factor (BDNF) is involved in synaptic development and plasticity, and alterations in BDNF expression or signaling are implicated in drug addiction and psychiatric diseases, such as depression and schizophrenia. In this study, we administered phencyclidine to postnatal and adult rats with different time schedules, and determined the correlations between BDNF expression and the behavioral effects. Both single and repeated phencyclidine injections into adult rats induced BDNF up-regulation in the corticolimbic system and a decrease in prepulse inhibition, both of which were transient. In contrast, subchronic postnatal administration increased BDNF protein and mRNA levels in the hippocampus and entorhinal cortex, which were sustained until 8 weeks of age. In parallel, the postnatal rats treated with phencyclidine developed a persistent decrease in prepulse inhibition at the adult stage. The chronic BDNF increase appeared to contribute to the prepulse inhibition abnormality, as subchronic BDNF infusion into the hippocampus of normal rats mimicked the prepulse inhibition deficits. This study suggests that phencyclidine exposure during brain development induces sustained BDNF up-regulation in the limbic system with a biological link to sensorimotor gating deficits.
脑源性神经营养因子（BDNF）参与突触发育和可塑性，BDNF表达或信号传导的改变与药物成瘾以及精神疾病如抑郁症和精神分裂症有关。在本研究中，我们以不同的时间安排给新生和成年大鼠施用苯环利定，并确定BDNF表达与行为效应之间的相关性。向成年大鼠单次和重复注射苯环利定均诱导皮质边缘系统中BDNF上调以及前脉冲抑制降低，两者均为短暂性。相比之下，新生期亚慢性给药增加了海马体和内嗅皮质中BDNF蛋白和mRNA水平，这种增加持续至8周龄。同时，用苯环利定处理的新生大鼠在成年期出现前脉冲抑制持续降低。慢性BDNF增加似乎导致了前脉冲抑制异常，因为向正常大鼠海马体中输注亚慢性BDNF模拟了前脉冲抑制缺陷。本研究表明，脑发育期间接触苯环利定会诱导边缘系统中BDNF持续上调，并与感觉运动门控缺陷存在生物学联系。
