Kiss Alexander, Søderman Andreas, Bundzikova Jana, Pirnik Zdeno, Mikkelsen Jens D
Laboratory of Functional Neuromorphology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska Street 3, 833 06 Bratislava, Slovakia.
Brain Res Bull. 2006 Dec 11;71(1-3):200-7. doi: 10.1016/j.brainresbull.2006.09.004. Epub 2006 Sep 27.
Functional activation of oxytocinergic (OXY) cells in the hypothalamic paraventricular (PVN), supraoptic (SON), and accessory (ACC) nuclei was investigated in response to acute treatment with Zolpidem (a GABA(A) receptor agonist with selectivity for alpha(1) subunits) utilizing dual Fos/OXY immunohistochemistry. Zolpidem was administered intraperitoneally in dose 10 mg/kg of BW and 60 min later the animals were sacrificed by transcardial perfusion with fixative. The Fos/OXY co-labelings were analyzed on 40 microm thick serial coronal sections using computerized light microscopy. Zolpidem elicited a concordant Fos/OXY staining in all four PVN sub-areas investigated, including the anterior (15.71+/-2.35%), middle (14.52+/-2.53%), dorsal (13.34+/-2.61%), and periventricular (18.21+/-4.75%) ones, however, had no significant stimulatory effect on OXY cells in the SON. In response to Zolpidem, statistically significant activations were also seen in certain groups of accessory structures including the circular nucleus (13.99+/-3.43%), small clusters of accessory neurons (10.55+/-1.94%), and the lateral hypothalamic perivascular nucleus (9.42+/-2.74%). Between the naive and vehicle controls, the dual Fos/OXY labelings did not elicit any significant differences. Our data provide insight into the topographic patterns of brain activity within the clusters of magnocellular OXY cells in the hypothalamus associated with stimulation of GABA(A) benzodiazepine receptors and for the first time illustrate the triggering contemporaneousness within the cells of the principal and accessory magnocellular nuclei in response to Zolpidem treatment. The present study provides a comparative background that may help in the further understanding of a possible extend of Zolpidem effect on the brain.
利用双Fos/OXY免疫组织化学方法,研究了下丘脑室旁核(PVN)、视上核(SON)和副核(ACC)中催产素能(OXY)细胞对唑吡坦(一种对α1亚基具有选择性的GABA(A)受体激动剂)急性治疗的功能激活情况。唑吡坦以10mg/kg体重的剂量腹腔注射,60分钟后通过心脏灌注固定液处死动物。使用计算机化光学显微镜在40微米厚的连续冠状切片上分析Fos/OXY共标记。唑吡坦在所研究的PVN的所有四个亚区域中均引发了一致的Fos/OXY染色,包括前部(15.71±2.35%)、中部(14.52±2.53%)、背部(13.34±2.61%)和室周部(18.21±4.75%),然而,对SON中的OXY细胞没有显著的刺激作用。对唑吡坦的反应中,在某些副结构组中也观察到了统计学上的显著激活,包括环核(13.99±3.43%)、副神经元小簇(10.55±1.94%)和下丘脑外侧血管周围核(9.42±2.74%)。在未处理组和溶剂对照组之间,双Fos/OXY标记没有引发任何显著差异。我们的数据深入了解了与GABA(A)苯二氮䓬受体刺激相关的下丘脑大细胞OXY细胞簇内的脑活动地形图模式,并首次说明了在唑吡坦治疗后,主副大细胞核细胞内的触发同步性。本研究提供了一个比较背景,可能有助于进一步理解唑吡坦对大脑影响的可能范围。