Morales Anne, Bonnet Chantal, Bourgoin Naïck, Touvier Thierry, Nadam Jérémie, Laglaine Aël, Navarro Fabrice, Moulin Colette, Georges Béatrice, Pequignot Jean-Marc, Bezin Laurent
Laboratoire de Physiologie Intégrative Cellulaire et Moléculaire, UMR 5123 CNRS and Université Claude Bernard Lyon 1, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France.
Brain Res. 2006 Sep 13;1109(1):164-75. doi: 10.1016/j.brainres.2006.06.075. Epub 2006 Aug 10.
Orexin-A (OX-A) and -B (OX-B) peptides present in the hippocampus are considered to be exclusively contained in fibers arising from hypothalamus neurons, which were established as the only source of orexins (OXs). Because OX-A is known to exert excitatory actions in the hippocampus, we hypothesized that the level of OXs targeted toward the hippocampus may be increased following status-epilepticus (SE)-induced epileptogenesis in the rat pilocarpine model of temporal lobe epilepsy. We found that tissue concentration of prepro-OX mRNA, which encodes for both peptides, rapidly decreased in the hypothalamus of rats having experienced pilocarpine-induced SE (Pilo-SE) followed by a reduced density of OX-A and OX-B immunopositive fibers arising from these neurons. By contrast, it was unexpected to detect within the hippocampus the presence of prepro-OX mRNA in basal conditions and to evidence its up-regulation during the 1- to 3-day period following Pilo-SE. The number of prepro-OX mRNA copies determined by real-time RT-PCR was approximately 50-fold lower in the hippocampus than that in the hypothalamus, precluding the use of in situ hybridization to localize the cells which synthesize the transcript within the hippocampus. The increase in prepro-OX mRNA level within the hippocampus was accompanied by the detection of OX-B-like immunoreactivity 2-3 days post-SE, not only in pyramidal neurons, granule cells and cell bodies resembling interneurons, but also in some astrocytes scattered throughout the hippocampus. The present data suggest that the gene encoding OXs can be activated in the hippocampus, which may play a role in the pathogenesis of epilepsy.
海马体中存在的食欲素A（OX-A）和食欲素B（OX-B）肽被认为仅包含在下丘脑神经元产生的纤维中，而下丘脑神经元被确定为食欲素（OXs）的唯一来源。由于已知OX-A在海马体中发挥兴奋作用，我们推测在大鼠毛果芸香碱颞叶癫痫模型中，癫痫持续状态（SE）诱导癫痫发生后，靶向海马体的OXs水平可能会升高。我们发现，编码这两种肽的前食欲素原mRNA的组织浓度在经历毛果芸香碱诱导的SE（Pilo-SE）的大鼠下丘脑迅速下降，随后这些神经元产生的OX-A和OX-B免疫阳性纤维密度降低。相比之下，在基础条件下在海马体中检测到前食欲素原mRNA的存在，并在Pilo-SE后的1至3天内证明其上调，这是出乎意料的。通过实时RT-PCR测定的海马体中前食欲素原mRNA拷贝数比下丘脑低约50倍，这使得无法使用原位杂交来定位海马体内合成转录本的细胞。海马体中前食欲素原mRNA水平的增加伴随着在SE后2至3天检测到OX-B样免疫反应性，不仅在锥体神经元、颗粒细胞和类似中间神经元的细胞体中，而且在整个海马体中散布的一些星形胶质细胞中也有检测到。目前的数据表明，编码OXs的基因可以在海马体中被激活，这可能在癫痫的发病机制中起作用。
