Brain-derived neurotrophic factor enhances fetal respiratory rhythm frequency in the mouse preBotzinger complex in vitro
Brain-derived neurotrophic factor enhances fetal respiratory rhythm frequency in the mouse preBotzinger complex in vitro
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DOI：
10.1111/j.1460-9568.2008.06345.x
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发表时间：
2008-08-01
影响因子：
3.4
通讯作者：
Thoby-Brisson, Muriel
中科院分区：
文献类型：
--
作者：
Bouvier, Julien;Autran, Sandra;Thoby-Brisson, Muriel
脑源性神经营养因子（BDNF）是需要在产前期间的呼吸中枢命令的正常发展，然而，其潜在的机制仍然未知。为了解决这个问题，本研究探讨了BDNF调节胎儿呼吸节律的产生在preBotzinger复杂（preBotC）的小鼠，从产前16.5天的动物获得的横向脑干切片。BDNF应用（100 ng/mL，15 min）使preBotC中节律性群体活动的频率增加了43%。当制剂暴露于神经生长因子（100 ng/mL，30 min）或用酪氨酸激酶抑制剂K252 a（1 h，200 nM）预处理时，未观察到这种效应，表明BDNF对preBotC活性的调节需要激活其同源酪氨酸受体激酶TrkB。与这一发现相一致，单细胞逆转录聚合酶链反应实验表明，三分之一的节奏活跃的preBotC神经元分析表达TrkB mRNA。此外，20%表达BDNF mRNA，表明preBotC既是BDNF的靶点，也是BDNF的来源。在网络水平，脑源性神经营养因子增强了preBotC谷氨酸能神经元的活性，并使呼吸神经元中的谷氨酸能突触驱动增强了34%。在细胞水平上，BDNF增加内源性爆发神经元的活动频率53.3%，但对呼吸跟随神经元的基底膜特性，包括Ih电流没有影响。我们的数据表明，BDNF信号通过TrkB可以急性调节胎儿的呼吸节律与增加的前BotC的神经元驱动和爆发活动。
Brain-derived neurotrophic factor (BDNF) is required during the prenatal period for normal development of the respiratory central command; however, the underlying mechanisms remain unknown. To approach this issue, the present study examined BDNF regulation of fetal respiratory rhythm generation in the preBotzinger complex (preBotC) of the mouse, using transverse brainstem slices obtained from prenatal day 16.5 animals. BDNF application (100 ng/mL, 15 min) increased the frequency of rhythmic population activity in the preBotC by 43%. This effect was not observed when preparations were exposed to nerve growth factor (100 ng/mL, 30 min) or pretreated with the tyrosine kinase inhibitor K252a (1 h, 200 nM), suggesting that BDNF regulation of preBotC activity requires activation of its cognate tyrosine receptor kinase, TrkB. Consistent with this finding, single-cell reverse transcription-polymerase chain reaction experiments showed that one third of the rhythmically active preBotC neurons analysed expressed TrkB mRNA. Moreover, 20% expressed BDNF mRNA, suggesting that the preBotC is both a target and a source of BDNF. At the network level, BDNF augmented activity of preBotC glutamatergic neurons and potentiated glutamatergic synaptic drives in respiratory neurons by 34%. At the cellular level, BDNF increased the activity frequency of endogenously bursting neurons by 53.3% but had no effect on basal membrane properties of respiratory follower neurons, including the Ih current. Our data indicate that BDNF signalling through TrkB can acutely modulate fetal respiratory rhythm in association with increased glutamatergic drive and bursting activity in the preBotC.