Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
Neuroscience. 2011 Jun 2;183:47-63. doi: 10.1016/j.neuroscience.2011.03.047. Epub 2011 Mar 29.
Corticotropin-releasing factor (CRF) and CRF-related neuropeptides are involved in the regulation of stress-related physiology and behavior. Members of the CRF family of neuropeptides bind to two known receptors, the CRF type 1 (CRF₁) receptor, and the CRF type 2 (CRF₂) receptor. Although the distribution of CRF₂ receptor mRNA expression has been extensively studied, the distribution of CRF₂ receptor protein has not been characterized. An area of the brain known to contain high levels of CRF₂ receptor mRNA expression and CRF₂ receptor binding is the dorsal raphe nucleus (DR). In the present study we investigated in detail the distribution of CRF₂ receptor immunoreactivity throughout the rostrocaudal extent of the DR. CRF₂ receptor-immunoreactive perikarya were observed throughout the DR, with the highest number and density in the mid-rostrocaudal DR. Dual immunofluorescence revealed that CRF₂ receptor immunoreactivity was frequently co-localized with tryptophan hydroxylase, a marker of serotonergic neurons. This study provides evidence that CRF₂ receptor protein is expressed in the DR, and that CRF₂ receptors are expressed in topographically organized subpopulations of cells in the DR, including serotonergic neurons. Furthermore, these data are consistent with the hypothesis that CRF₂ receptors play an important role in the regulation of stress-related physiology and behavior through actions on serotonergic and non-serotonergic neurons within the DR.
促肾上腺皮质释放因子（CRF）和 CRF 相关神经肽参与应激相关生理和行为的调节。CRF 家族神经肽的成员与两种已知的受体结合，即 CRF 型 1（CRF₁）受体和 CRF 型 2（CRF₂）受体。尽管已经广泛研究了 CRF₂ 受体 mRNA 表达的分布，但 CRF₂ 受体蛋白的分布尚未得到表征。已知含有高水平 CRF₂ 受体 mRNA 表达和 CRF₂ 受体结合的脑区是中脑背缝核（DR）。在本研究中，我们详细研究了 CRF₂ 受体免疫反应性在 DR 的头尾延伸中的分布。在整个 DR 中观察到 CRF₂ 受体免疫反应性的神经元，其中中 DR 的数量和密度最高。双重免疫荧光显示，CRF₂ 受体免疫反应性经常与色氨酸羟化酶共定位，色氨酸羟化酶是血清素能神经元的标志物。这项研究提供了证据表明，CRF₂ 受体蛋白在 DR 中表达，并且 CRF₂ 受体在 DR 中以拓扑组织的细胞亚群中表达，包括血清素能神经元。此外，这些数据与以下假设一致，即 CRF₂ 受体通过在 DR 内的血清素能和非血清素能神经元上的作用，在应激相关生理和行为的调节中发挥重要作用。
