JTP-2942, a novel thyrotropin-releasing hormone analogue, protects against spinal motor neuron degeneration in the wobbler mouse.
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.
The Fourth Department of Internal Medicine, Toho University Ohashi Hospital, Tokyo, Japan.
K
K
Ikeda
Y
Y
Iwasaki
M
M
Kinoshita
D000818:Animals; D051379:Mice; D008818:Mice, Neurologic Mutants; D016472:Motor Neuron Disease / Q000503:physiopathology / Q000517:prevention & control*; D009410:Nerve Degeneration / Q000503:physiopathology / Q000517:prevention & control*; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
C080784:JTP 2942; D013973:Thyrotropin-Releasing Hormone