Kiessling M, Xie Y, Kleihues P
Brain Res. 1984 Mar 26;296(1):1-13. doi: 10.1016/0006-8993(84)90506-7.
Protein synthesis was investigated in rats subjected to 30 min of bicuculline-induced seizures using biochemical and autoradiographic techniques. Incorporation studies were performed on freely convulsive animals following systemic administration of either a tracer dose of L-[1-14C]tyrosine or a flooding dose (7.5 mmol/kg) of L-[1-14C]valine. Using a tracer dose, amino acid incorporation was only moderately reduced (forebrain) or slightly enhanced (cerebellum/brainstem and spinal cord) but the specific radioactivity of [14C]tyrosine in the acid-soluble pool was increased 3- to 5-fold in experimental animals. After a flooding dose of [14C]valine the specific activity of the precursor amino acid was similar in control and convulsed animals. Under these conditions incorporation rates in forebrain and cerebellum/brainstem were reduced to 54 and 75%, respectively. Reduction of amino acid incorporation was even more pronounced in extraneural tissues, e.g. liver (6%), intestine (14%) and kidney (15%). Inhibition of protein synthesis in forebrain and cerebellum/brainstem was paralleled by a similar extent of polyribosome disaggregation in these regions (53 adn 78% of controls). In anaesthetized, mechanically ventilated rats, 30 min of seizure activity reduced forebrain polyribosomes to a similar extent (57%). Extraneural (hepatic) protein synthesis was also affected in physiologically controlled rats, but cerebellar polysomes were completely preserved. Autoradiographic studies using 3H-labelled amino acids were carried out to identify nerve cell populations most heavily affected. In freely convulsive rats both tracer dose and pool overloading revealed a similar regional pattern with preferential inhibition of amino acid incorporation in forebrain cortex, thalamus and the pyramidal cell layer of the hippocampus. These sites were also affected in the physiologically controlled animal, but the focal distribution of hippocampal and thalamic neurones with reduced protein synthesis differed from that in freely convulsive rats.
利用生化和放射自显影技术，对接受了30分钟荷包牡丹碱诱导癫痫发作的大鼠的蛋白质合成进行了研究。在全身给予示踪剂量的L-[1-14C]酪氨酸或过量剂量（7.5 mmol/kg）的L-[1-14C]缬氨酸后，对自由惊厥的动物进行掺入研究。使用示踪剂量时，氨基酸掺入仅适度减少（前脑）或略有增加（小脑/脑干和脊髓），但实验动物中酸溶性池内[14C]酪氨酸的比放射性增加了3至5倍。给予过量剂量的[14C]缬氨酸后，对照动物和惊厥动物中前体氨基酸的比活性相似。在这些条件下，前脑和小脑/脑干中的掺入率分别降至54%和75%。氨基酸掺入的减少在神经外组织中更为明显，例如肝脏（6%）、肠道（14%）和肾脏（15%）。前脑和小脑/脑干中蛋白质合成的抑制与这些区域中多核糖体解聚的相似程度平行（分别为对照的53%和78%）。在麻醉、机械通气的大鼠中，30分钟的癫痫发作活动使前脑多核糖体减少到相似程度（57%）。在生理状态受控的大鼠中，神经外（肝脏）蛋白质合成也受到影响，但小脑多核糖体完全保留。使用3H标记氨基酸进行放射自显影研究，以确定受影响最严重的神经细胞群体。在自由惊厥的大鼠中，示踪剂量和池过载均显示出相似的区域模式，前脑皮质、丘脑和海马锥体细胞层中氨基酸掺入受到优先抑制。这些部位在生理状态受控的动物中也受到影响，但蛋白质合成减少的海马和丘脑神经元的局灶分布与自由惊厥大鼠不同。
