JTP-2942, a novel thyrotropin-releasing hormone analogue, protects against spinal motor neuron degeneration in the wobbler mouse.

Abstract

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.

• Authors: K Ikeda, Y Iwasaki, M Kinoshita
• Journal: Neuroscience letters (Neurosci Lett) Vol. 250 Issue 1 Pg. 9-12 (Jun 26 1998) ISSN: 0304-3940 [Print] Ireland
• PMID: 9696053 (Publication Type: Journal Article)

Chemical References

• JTP 2942
• Thyrotropin-Releasing Hormone

Topics

• Animals
• Mice
• Mice, Neurologic Mutants
• Motor Neuron Disease (physiopathology, prevention & control)
• Nerve Degeneration (physiopathology, prevention & control)
• Spinal Cord (drug effects, physiopathology)
• Thyrotropin-Releasing Hormone (analogs & derivatives, pharmacology, therapeutic use)