Ebling F J, Maywood E S, Mehta M, Hancock D C, McNulty S, De Bono J, Bray S J, Hastings M H
Department of Anatomy, University of Cambridge, UK.
Brain Res Bull. 1996;41(5):257-68. doi: 10.1016/s0361-9230(96)00192-x.
The suprachiasmatic nucleus (SCN) generates circadian rhythms of behavior and hormone secretion in mammals, and integrates responses to light and nonphotic stimuli to synchronize such rhythms with the external environment. Previous studies have demonstrated a close association between the induction of the immediate early gene (IEG) c-fos in the SCN by light and phase shifts of circadian rhythms induced by light, but nonphotic stimuli (e.g., arousal), which also cause phase shifts, do not increase c-fos expression in the SCN. Because c-fos is now known to be a member of a large family of IEGs which can regulate transcription and thus cellular function, the aim of the current study was to determine whether induction of another member of this immediate early gene family, fosB, is associated with photic and nonphotic phase shifts. An antiserum that recognizes a unique peptide sequence derived from FosB was produced so that the expression of fosB could be investigated in cells within the SCN by immunocytochemical detection of its protein product. The regional distribution of FosB-immunoreactive (ir) cells in the SCN of Syrian and Siberian hamsters was broadly similar to that for c-Fos-ir cells. However, whereas c-fos expression in the SCN was constitutively low, but could be massively induced by light at particular circadian phases, FosB-ir cells were present at all circadian phases studied, irrespective of photic stimulation, and light only produced marginal increases in the number of FosB-ir cells compared with nonstimulated controls. Moreover, blockade of glutamatergic neurotransmission by pretreatment of hamsters with the NMDA receptor antagonist MK801 significantly reduced photic induction of c-Fos-ir cells, but did not influence the number of FosB-ir cells in the SCN. Finally, an arousing nonphotic stimulus known to cause phase advances in wheel-running behavior in Syrian hamsters did not alter significantly the number of FosB-ir cells in the SCN. These observations indicate that light and nonphotic stimuli are not potent regulators of fosB expression in the SCN. However, because fosB and c-fos can be present in the SCN at the same time after a light pulse, these studies indicate the potential for interactions with each other and with members of the Jun family in the regulation of the circadian timing system.
视交叉上核(SCN)控制着哺乳动物行为和激素分泌的昼夜节律,并整合对光和非光刺激的反应,使这些节律与外部环境同步。先前的研究表明,光诱导SCN中即刻早期基因(IEG)c-fos与光诱导的昼夜节律相移之间存在密切关联,但同样会引起相移的非光刺激(如唤醒)并不会增加SCN中c-fos的表达。由于现在已知c-fos是一个大型IEG家族的成员,该家族可调节转录进而调控细胞功能,因此本研究的目的是确定该即刻早期基因家族的另一个成员fosB的诱导是否与光和非光相移有关。制备了一种能识别源自FosB的独特肽序列的抗血清,以便通过免疫细胞化学检测其蛋白产物来研究SCN内细胞中fosB的表达。叙利亚仓鼠和西伯利亚仓鼠SCN中FosB免疫反应性(ir)细胞的区域分布与c-Fos-ir细胞的大致相似。然而,SCN中c-fos的表达本底较低,但在特定昼夜节律阶段可被光大量诱导,而FosB-ir细胞在所研究的所有昼夜节律阶段均存在,与光刺激无关,并且与未受刺激的对照组相比,光仅使FosB-ir细胞数量略有增加。此外,用NMDA受体拮抗剂MK801预处理仓鼠以阻断谷氨酸能神经传递,可显著降低光诱导的c-Fos-ir细胞数量,但不影响SCN中FosB-ir细胞的数量。最后,一种已知会使叙利亚仓鼠的轮转行为发生相位提前的唤醒性非光刺激,并未显著改变SCN中FosB-ir细胞的数量。这些观察结果表明,光和非光刺激并非SCN中fosB表达的有效调节因子。然而,由于在光脉冲后fosB和c-fos可同时存在于SCN中,这些研究表明它们在昼夜节律计时系统的调节中可能相互作用,并与Jun家族成员相互作用。