Ikeda K, Iwasaki Y, Kinoshita M
The Fourth Department of Internal Medicine, Toho University Ohashi Hospital, Tokyo, Japan.
Neurosci Lett. 1998 Jun 26;250(1):9-12. doi: 10.1016/s0304-3940(98)00389-9.
JTP-2942, a novel thyrotropin-releasing hormone (TRH) analogue, exhibits a strong acetylcholine release-enhancing effect in the rat hippocampus and frontal cortex. This molecule has a more powerful and prolonged action on cholinergic neurons than TRH. Here we studied whether JTP-2942 treatment can ameliorate motor dysfunction and spinal motor neuron degeneration in the wobbler mouse. After clinical diagnosis at postnatal age 3-4 weeks, wobbler mice received intraperitoneal injections of JTP-2942 (2 mg/kg per day) for 4 weeks (long-term treatment) or 2 weeks (short-term treatment), TRH (50 mg/kg per day) for 4 weeks or vehicle in a blind fashion. Compared with the vehicle, long-term administration of JTP-2942 potentiated grip strength, attenuated muscle contractures in the forelimbs, reduced denervation muscle atrophy and protected spinal motor neurons. After cessation of JTP-2942 (short-term treatment), motor dysfunction deteriorated rapidly. Symptomatic and neuropathological progression were not retarded in mice that received TRH or short-term JTP-2942 treatment. Our results indicate that JTP-2942 may have therapeutic potential for lower motor neuron disease or motor neuropathy.
JTP - 2942是一种新型促甲状腺激素释放激素（TRH）类似物，在大鼠海马体和额叶皮质中表现出强大的增强乙酰胆碱释放的作用。该分子对胆碱能神经元的作用比TRH更强大且持久。在此，我们研究了JTP - 2942治疗是否能改善震颤小鼠的运动功能障碍和脊髓运动神经元变性。在出生后3 - 4周进行临床诊断后，震颤小鼠被随机分为四组，分别接受为期4周（长期治疗）或2周（短期治疗）的腹腔注射JTP - 2942（每天2 mg/kg）、为期4周的腹腔注射TRH（每天50 mg/kg）或注射溶媒。与溶媒组相比，长期给予JTP - 2942可增强握力，减轻前肢肌肉挛缩，减少失神经肌肉萎缩并保护脊髓运动神经元。停止给予JTP - 2942（短期治疗）后，运动功能障碍迅速恶化。接受TRH或短期JTP - 2942治疗的小鼠，其症状和神经病理学进展并未得到延缓。我们的结果表明，JTP - 2942可能对下运动神经元疾病或运动神经病具有治疗潜力。
