Pavelock Kristen A, Girard Beatrice M, Schutz Kristin C, Braas Karen M, May Victor
Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
J Neurochem. 2007 Feb;100(3):603-16. doi: 10.1111/j.1471-4159.2006.04293.x. Epub 2006 Dec 1.
Among bone morphogenetic proteins (BMPs), the decapentaplegic (Dpp; BMP2, BMP4) and glass bottom boat (Gbb/60A; BMP5, BMP6, BMP7) subgroups have well-described functions guiding autonomic and sensory neuronal development, fiber formation and neurophenotypic identities. Evaluation of rat superior cervical ganglia (SCG) post-ganglionic sympathetic neuron developmental regulators identified that selected BMPs of the transforming growth factor beta superfamily have reciprocal effects on neuronal pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) expression. Dpp and Gbb/60A BMPs rapidly down-regulated PACAP expression, while up-regulating other sympathetic neuropeptides, including PACAP-related VIP. The suppressive effects of BMP on PACAP mRNA and peptide expression were potent, efficacious and phosphorylated mothers against decapentaplegic homolog (Smad) signaling-dependent. Axotomy of SCG dramatically increases PACAP expression, and the possibility that abrogation of inhibitory retrograde target tissue BMP signaling may contribute to this up-regulation of sympathetic neuron PACAP was investigated. Replacement of BMP6 to SCG explant preparations significantly blunted the injury-induced elevated PACAP expression, with a concomitant decrease in sympathetic PACAP-immunoreactive neuron numbers. These studies suggested that BMPs modulate neuropeptide identity and diversity by stimulating or restricting the expression of specific peptidergic systems. Furthermore, the liberation of SCG neurons from target-derived BMP inhibition following axotomy may be one participating mechanism associated with injury-induced neuropeptidergic plasticity.
在骨形态发生蛋白（BMPs）中，果蝇的“截瘫蛋白”（Dpp；BMP2、BMP4）和“玻璃底船蛋白”（Gbb/60A；BMP5、BMP6、BMP7）亚组具有明确的功能，可引导自主神经和感觉神经元的发育、纤维形成以及神经表型特征。对大鼠颈上神经节（SCG）节后交感神经元发育调节因子的评估表明，转化生长因子β超家族中特定的BMPs对神经元垂体腺苷酸环化酶激活多肽（PACAP）和血管活性肠肽（VIP）的表达具有相互作用。Dpp和Gbb/60A BMPs迅速下调PACAP的表达，同时上调包括PACAP相关的VIP在内的其他交感神经肽。BMP对PACAP mRNA和肽表达的抑制作用强大、有效且依赖于磷酸化的“抗截瘫同源蛋白”（Smad）信号传导。切断SCG会显著增加PACAP的表达，因此研究了消除逆行性靶组织抑制性BMP信号传导是否可能导致交感神经元PACAP的这种上调。将BMP6替换到SCG外植体制备物中可显著减弱损伤诱导的PACAP表达升高，同时交感神经PACAP免疫反应性神经元数量减少。这些研究表明，BMPs通过刺激或限制特定肽能系统的表达来调节神经肽的特征和多样性。此外，切断轴突后SCG神经元从靶源性BMP抑制中释放出来可能是与损伤诱导的神经肽可塑性相关的一种参与机制。
