Princivalle Alessandra P, Richards Douglas A, Duncan John S, Spreafico Roberto, Bowery Norman G
Department of Pharmacology, Division of Neuroscience, University of Birmingham, The Medical School, Birmingham B15 2TT, UK.
Epilepsy Res. 2003 Jun-Jul;55(1-2):39-51. doi: 10.1016/s0920-1211(03)00090-1.
In the present study, we have investigated GABA(B) receptor expression in somatosensory cortex (S1) and the ventrobasal (VB) and reticular (Rt) thalamic nuclei of Genetic Absence Epilepsy Rats from Strasbourg (GAERS), which represent an animal model for the human absence epilepsy. We focused our attention on the thalamocortical network because it has been demonstrated that absence seizures are generated in this specific circuit, which is under the control of several inhibitory, e.g. GABA, and excitatory systems. Autoradiography data obtained with the GABA(B) receptor antagonist [3H]CGP62349 did not show any differences in Kd or Bmax values between control rats and GAERS. In situ hybridisation (ISH) results showed a significant increase in messenger RNA for GABA(B1) in the S1 and a decrease in the VB thalamic nucleus but not in the Rt thalamic nucleus. By contrast the immunocytochemical data revealed an increased expression of both GABA(B1) and GABA(B2) receptor subunits in all the regions examined, somatosensory cerebral cortex, VB thalamus and Rt nucleus in GAERS compared to controls. The main finding was an up-regulation of GABA(B) receptor protein in the corticothalamic circuit in GAERS compared to controls.
在本研究中，我们调查了来自斯特拉斯堡的遗传性失神癫痫大鼠（GAERS）的体感皮层（S1）、腹侧基底（VB）和网状（Rt）丘脑核中GABA(B)受体的表达情况，GAERS代表了人类失神癫痫的一种动物模型。我们将注意力集中在丘脑皮质网络上，因为已经证明失神发作是在这个特定的回路中产生的，该回路受多种抑制性系统（如GABA）和兴奋性系统的控制。用GABA(B)受体拮抗剂[3H]CGP62349获得的放射自显影数据显示，对照大鼠和GAERS之间的Kd或Bmax值没有任何差异。原位杂交（ISH）结果显示，S1中GABA(B1)信使核糖核酸显著增加，VB丘脑核中减少，但Rt丘脑核中没有变化。相比之下，免疫细胞化学数据显示，与对照组相比，GAERS中所有检测区域（体感大脑皮层、VB丘脑和Rt核）的GABA(B1)和GABA(B2)受体亚基表达均增加。主要发现是，与对照组相比，GAERS的皮质丘脑回路中GABA(B)受体蛋白上调。
