Dipartimento di Medicina Molecolare, Università La Sapienza, Roma, Italy.
Stress. 2012 Jul;15(4):378-84. doi: 10.3109/10253890.2011.627071. Epub 2012 Jan 4.
Nociceptin/orphanin FQ (N/OFQ) peptide and its receptor are not only ubiquitously expressed in mammalian brain and spinal cord but are also abundant in limbic structures, particularly in the hippocampus. The widespread distribution of N/OFQ reflects the broad spectrum of its biological actions such as nociception, food intake, spontaneous locomotor activity, and learning and memory processes. Since the hippocampus is involved in the control of adrenocortical activity, its role in stress-related phenomena is well characterized. In male Wistar rats, we first examined the effects of acute restraint stress (120 min) on the brain immunohistochemical localization of N/OFQ. The analysis carried out on sections obtained at the onset of stress revealed enhanced expression of N/OFQ in CA1, CA3, and the dentate gyrus as well as increased plasma corticosterone concentrations. Next, we examined whether endogenous glucocorticoid hormone plays a role in the modulation of hippocampal N/OFQ expression in response to stress. To this end, rats were injected with corticosterone (1 mg/kg) or subjected to restraint stress 1 week after adrenalectomy. Two hours after corticosterone administration, plasma glucocorticoid concentrations were comparable to those observed after restraint stress, while N/OFQ expression had significantly increased in all the hippocampal subfields examined. By contrast, in adrenalectomized rats, stress did not modify protein expression. These results confirm that stress can affect N/OFQ expression and that glucocorticoids may constitute hormonal mediators of this complex interplay.
孤啡肽(Nociceptin/orphanin FQ,N/OFQ)肽及其受体不仅在哺乳动物的大脑和脊髓中广泛表达,而且在边缘结构中也大量存在,特别是在海马体中。N/OFQ 的广泛分布反映了其广泛的生物学作用,如疼痛感知、食物摄入、自发运动活动以及学习和记忆过程。由于海马体参与了肾上腺皮质活动的控制,其在应激相关现象中的作用得到了很好的描述。在雄性 Wistar 大鼠中,我们首先研究了急性束缚应激(120 分钟)对 N/OFQ 脑免疫组织化学定位的影响。在应激开始时获得的切片上进行的分析显示,CA1、CA3 和齿状回中的 N/OFQ 表达增强,同时血浆皮质酮浓度升高。接下来,我们研究了内源性糖皮质激素是否在应激对海马 N/OFQ 表达的调节中发挥作用。为此,我们给大鼠注射皮质酮(1 毫克/千克)或在肾上腺切除后 1 周进行束缚应激。皮质酮给药后 2 小时,血浆糖皮质激素浓度与束缚应激后观察到的浓度相当,而所有检查的海马亚区中的 N/OFQ 表达均显著增加。相比之下,在肾上腺切除大鼠中,应激并未改变蛋白质表达。这些结果证实应激可以影响 N/OFQ 的表达,而糖皮质激素可能是这种复杂相互作用的激素介导物。