Hermanson O, Larhammar D, Blomqvist A
Department of Biomedicine and Surgery, Faculty of Health Sciences, University of Linköping, Sweden.
J Comp Neurol. 1998 Oct 19;400(2):255-70.
The pontine parabrachial nucleus (PB) is a major target for ascending fibers from nociresponsive dorsal horn neurons. Several different neuropeptides have been identified in the PB. By using double-labeling methods that combine in situ hybridization histochemistry with retrograde tract tracing and immunohistochemistry, we have examined the subnuclear localization of preprocholecystokinin mRNA (ppCCK)-containing neurons, investigated their efferent projection, and analyzed their expression of intracellular signaling substances that may be of importance for nociceptive processing. The results show that neurons containing ppCCK are preferentially localized to the superior lateral subnucleus (PBsl), whereas other subnuclei, such as the dorsal lateral, external lateral, central lateral, and ventral lateral subnuclei, and the Kölliker-Fuse nucleus, contain only moderate to small numbers of such neurons. Injections of the retrograde tracer cholera toxin subunit b into the ventromedial hypothalamus demonstrated that ppCCK-containing neurons in PBsl were projection neurons. Following nociceptive stimulation, the ppCCK-containing neurons expressed FOS protein as well as phosphorylated cyclic AMP-responsive element-binding protein (CREB). In addition, Ca2+/calmodulin-dependent kinase II (CaMKII) was heavily and rather selectively expressed in PBsl and was co-localized to ppCCK-containing neurons. These observations show that nociceptive stimuli activate a cholecystokinin pathway from the parabrachial nucleus to the ventromedial hypothalamus that may be important for homeostatic responses to tissue damage, and point to a putative intracellular route for Ca2+-mediated FOS transcription via CaMKII and CREB for the regulation of ppCCK transcription.
脑桥臂旁核（PB）是伤害性反应性背角神经元上行纤维的主要靶点。在PB中已鉴定出几种不同的神经肽。通过使用将原位杂交组织化学与逆行束路追踪和免疫组织化学相结合的双重标记方法，我们研究了含前胆囊收缩素原mRNA（ppCCK）的神经元的亚核定位，研究了它们的传出投射，并分析了它们对伤害性处理可能重要的细胞内信号物质的表达。结果表明，含ppCCK的神经元优先定位于上外侧亚核（PBsl），而其他亚核，如背外侧、外侧、中央外侧和腹外侧亚核以及 Kölliker-Fuse 核，仅含有少量此类神经元。将逆行示踪剂霍乱毒素亚基b注射到腹内侧下丘脑表明，PBsl中含ppCCK的神经元是投射神经元。伤害性刺激后，含ppCCK的神经元表达FOS蛋白以及磷酸化的环磷酸腺苷反应元件结合蛋白（CREB）。此外，Ca2+/钙调蛋白依赖性激酶II（CaMKII）在PBsl中大量且相当选择性地表达，并与含ppCCK的神经元共定位。这些观察结果表明，伤害性刺激激活了一条从臂旁核到腹内侧下丘脑的胆囊收缩素通路，这可能对组织损伤的稳态反应很重要，并指出了一条通过CaMKII和CREB进行Ca2+介导的FOS转录以调节ppCCK转录的假定细胞内途径。
