Scordalakes Elka M, Yue Chunmei, Gainer Harold
Laboratory of Neurochemistry, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, MD, USA.
Prog Brain Res. 2008;170:43-51. doi: 10.1016/S0079-6123(08)00404-4.
Intron-specific probes measure heteronuclear RNA (hnRNA) levels and thus approximate the transcription rates of genes, in part because of the rapid turnover of this intermediate form of RNA in the cell nucleus. Previously, we used oxytocin (Oxt)- and vasopressin (Avp)- intron-specific riboprobes to measure changes in Oxt and Avp hnRNA levels in the supraoptic nucleus (SON) by quantitative in situ hybridization (ISH) after various classical physiological perturbations, including acute and chronic salt loading, and lactation. In the present experiments, we used a novel experimental model to study the neurotransmitter regulation of Oxt and Avp gene expression in the rat SON in vivo. Bilateral cannulae connected via tubing to Alzet osmotic mini-pumps were positioned over the SON. In every experiment, one SON was infused with PBS and served as the control SON in each animal, and the contralateral SON received infusions of various neurotransmitter agonists and antagonists. Using this approach, we found that Avp but not Oxt gene expression increased after acute (2-5h) combined excitatory amino acid agonist and GABA antagonist treatment, similar to what we found after an acute hyperosmotic stimulus. Since both OXT and AVP are known to be comparably and robustly secreted in response to acute osmotic stimuli in vivo and glutamate agonists in vitro, our results indicate a dissociation between OXT secretion and Oxt gene transcription in vivo.
内含子特异性探针可测量异核RNA(hnRNA)水平,从而近似估算基因的转录速率,部分原因是这种RNA的中间形式在细胞核中周转迅速。此前,我们使用催产素(Oxt)和加压素(Avp)的内含子特异性核糖探针,通过定量原位杂交(ISH)技术,在各种经典生理扰动(包括急性和慢性盐负荷以及泌乳)后,测量视上核(SON)中Oxt和Avp的hnRNA水平变化。在本实验中,我们使用了一种新型实验模型,来研究体内大鼠视上核中Oxt和Avp基因表达的神经递质调控。通过管道连接到Alzet渗透微型泵的双侧套管置于视上核上方。在每个实验中,每只动物的一个视上核注入磷酸盐缓冲液(PBS)作为对照视上核,对侧视上核则注入各种神经递质激动剂和拮抗剂。使用这种方法,我们发现,急性(2 - 5小时)联合兴奋性氨基酸激动剂和GABA拮抗剂处理后,Avp基因表达增加,而Oxt基因表达未增加,这与我们在急性高渗刺激后发现的情况类似。由于已知OXT和AVP在体内对急性渗透刺激以及体外对谷氨酸激动剂的反应中分泌相当且强烈,我们的结果表明体内OXT分泌与Oxt基因转录之间存在解离。