Department of Behavioral Neurogenomics, Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia.
Neurosci Lett. 2013 Aug 29;550:115-8. doi: 10.1016/j.neulet.2013.06.056. Epub 2013 Jul 3.
Prepulse inhibition (PPI), the reduction in acoustic startle reflex when it is preceded by weak prepulse stimuli, is a measure of critical to normal brain functioning sensorimotor gating. PPI deficit was shown in a variety of psychiatric disorders including schizophrenia, and in DBA/2J mouse strain. In the current study, we examined the effects of brain-derived (BDNF) and glial cell line-derived (GDNF) neurotrophic factors on acoustic startle response and PPI in DBA/2J mice. It was found that BDNF (300 ng, i.c.v.) significantly increased amplitude of startle response and restored disrupted PPI in 7 days after acute administration. GDNF (800 ng, i.c.v.) did not produce significant alteration neither in amplitude of startle response nor in PPI in DBA/2J mice. The reversal effect of BDNF on PPI deficit was unusually long-lasting: significant increase in PPI was found 1.5 months after single acute BDNF administration. Long-term ameliorative effect BDNF on disrupted PPI suggested the implication of epigenetic mechanism in BDNF action on neurogenesis. BDNF rather than GDNF could be a perspective drug for the treatment of sensorimotor gating impairments.
前脉冲抑制（PPI），即当弱前脉冲刺激时，听觉惊跳反射的减少，是正常大脑功能感觉门控的关键指标。在包括精神分裂症在内的各种精神障碍以及 DBA/2J 小鼠品系中，都发现了 PPI 缺陷。在当前的研究中，我们研究了脑源性神经营养因子（BDNF）和神经胶质细胞衍生神经营养因子（GDNF）对 DBA/2J 小鼠听觉惊跳反应和 PPI 的影响。结果发现，BDNF（300ng，侧脑室注射）在急性给药后 7 天内显著增加了惊跳反应的幅度，并恢复了 PPI 的中断。GDNF（800ng，侧脑室注射）对 DBA/2J 小鼠的惊跳反应幅度和 PPI 均无显著改变。BDNF 对 PPI 缺陷的逆转效应异常持久：单次急性 BDNF 给药 1.5 个月后，发现 PPI 显著增加。BDNF 对 PPI 中断的长期改善作用表明，表观遗传机制在 BDNF 对神经发生的作用中具有重要意义。BDNF 而不是 GDNF 可能成为治疗感觉运动门控障碍的有前途的药物。
