Spencer C M, Houpt T A
Department of Biological Science and Program in Neuroscience, The Florida State University, BRF 209, Tallahassee, FL 32306-4340, USA.
Brain Res Mol Brain Res. 2001 Sep 30;93(2):113-26. doi: 10.1016/s0169-328x(01)00173-5.
Lithium is commonly used as a treatment for affective disorders in humans and as a toxin to produce conditioned taste aversions in rats. LiCl administration in rats has been correlated with activation of c-fos and cAMP-mediated gene transcription in many brain regions; however, little is known about the timing or duration of gene activation. We hypothesized that c-fos gene transcription is rapidly stimulated by LiCl, followed later by the expression of the inducible cAMP early repressor (ICER) transcription factor, a negative modulator of cAMP-mediated gene transcription. By in situ hybridization, we analyzed the timecourse of c-fos and ICER mRNA expression in the central nucleus of the amygdala (CeA), the paraventricular nucleus of the hypothalamus (PVN) and the supraoptic nucleus (SON) at seven time points (0, 0.3, 1, 3, 6, 9 and 12 h) after intraperitoneal LiCl injection (0.15 M, 12 ml/kg, 76 mg/kg). Expression of c-fos mRNA peaked between 20 min and 1 h and returned to baseline by 3 h in the CeA, PVN and SON. ICER mRNA was detected in these regions at 20 min, peaked at 1-3 h and returned to nearly baseline 9 h following LiCl injection. The time lag between c-fos mRNA expression and ICER mRNA expression within the same regions is consistent with ICER terminating c-fos gene transcription. However, no refractory period was detected for restimulation of c-fos transcription by a second injection of LiCl during the period of peak ICER mRNA expression, suggesting the involvement of other transcriptional modulators.
锂常用于治疗人类情感障碍，也作为一种毒素用于在大鼠中诱导条件性味觉厌恶。给大鼠注射氯化锂与许多脑区中c-fos的激活以及cAMP介导的基因转录相关；然而，关于基因激活的时间或持续时间知之甚少。我们假设氯化锂能迅速刺激c-fos基因转录，随后诱导型cAMP早期阻遏物（ICER）转录因子表达，ICER是cAMP介导的基因转录的负调节因子。通过原位杂交，我们分析了腹腔注射氯化锂（0.15 M，12 ml/kg，76 mg/kg）后7个时间点（0、0.3、1、3、6、9和12小时）杏仁核中央核（CeA）、下丘脑室旁核（PVN）和视上核（SON）中c-fos和ICER mRNA表达的时间进程。在CeA、PVN和SON中，c-fos mRNA表达在20分钟至1小时达到峰值，并在3小时恢复到基线水平。ICER mRNA在20分钟时在这些区域被检测到，在1 - 3小时达到峰值，并在注射氯化锂后9小时恢复到接近基线水平。同一区域内c-fos mRNA表达和ICER mRNA表达之间的时间间隔与ICER终止c-fos基因转录一致。然而，在ICER mRNA表达峰值期间，第二次注射氯化锂重新刺激c-fos转录时未检测到不应期，这表明其他转录调节因子也参与其中。
