Martin Jessica L, Jenkins Victoria K, Hsieh Hui-ya, Balkowiec Agnieszka
Department of Integrative Biosciences, Oregon Health and Science University, Portland, OR 97239, USA.
J Neurochem. 2009 Jan;108(2):450-64. doi: 10.1111/j.1471-4159.2008.05781.x. Epub 2008 Nov 29.
Functional characteristics of the arterial baroreceptor reflex change throughout ontogenesis, including perinatal adjustments of the reflex gain and adult resetting during hypertension. However, the cellular mechanisms that underlie these functional changes are not completely understood. Here, we provide evidence that brain-derived neurotrophic factor (BDNF), a neurotrophin with a well-established role in activity-dependent neuronal plasticity, is abundantly expressed in vivo by a large subset of developing and adult rat baroreceptor afferents. Immunoreactivity to BDNF is present in the cell bodies of baroafferent neurons in the nodose ganglion, their central projections in the solitary tract, and terminal-like structures in the lower brainstem nucleus tractus solitarius. Using ELISA in situ combined with electrical field stimulation, we show that native BDNF is released from cultured newborn nodose ganglion neurons in response to patterns that mimic the in vivo activity of baroreceptor afferents. In particular, high-frequency bursting patterns of baroreceptor firing, which are known to evoke plastic changes at baroreceptor synapses, are significantly more effective at releasing BDNF than tonic patterns of the same average frequency. Together, our study indicates that BDNF expressed by first-order baroreceptor neurons is a likely mediator of both developmental and post-developmental modifications at first-order synapses in arterial baroreceptor pathways.
动脉压力感受器反射的功能特性在个体发育过程中会发生变化,包括围产期反射增益的调整以及高血压成年期的重新设定。然而,这些功能变化背后的细胞机制尚未完全了解。在这里,我们提供证据表明,脑源性神经营养因子(BDNF),一种在依赖活动的神经元可塑性中具有既定作用的神经营养因子,在发育中的和成年大鼠的大量压力感受器传入神经元体内大量表达。在结状神经节中,压力感受器传入神经元的细胞体、它们在孤束中的中央投射以及延髓孤束核中的终末样结构都存在对BDNF的免疫反应性。使用原位ELISA结合电场刺激,我们表明天然BDNF从培养的新生结状神经节神经元中释放出来,以响应模拟压力感受器传入神经元体内活动的模式。特别是,已知能在压力感受器突触处引起可塑性变化的压力感受器高频爆发模式,在释放BDNF方面比相同平均频率的强直模式显著更有效。总之,我们的研究表明,一级压力感受器神经元表达的BDNF可能是动脉压力感受器通路中一级突触发育和发育后修饰的介质。