Kiyoshi Kinoshita, Yumi Watanabe, Hidetoshi Asai and Yuzo Matsuoka
Pharmacology Department, Discovery Research Laboratory, Tanabe Seiyaku
Co., Ltd.,
Kawagishi 2-2-50, Toda, Saitama 335-8505, Japan
Abstract: Although 3-acetylpyridine (3-AP) induces several motor
disturbances and it degenerates the olivocerebellar pathway, abnormalities
caused by 3-AP in cerebral motor regions remain to be elucidated. Here we
investigated the metabolic changes caused by 3-AP (75ﾊmg/kg,ﾊi.p.) on local
cerebral glucose utilization (LCGU) in various brain regions. The effects
of anti-ataxic agents, thyrotropin-releasing hormone (TRH) (10ﾊmg/kg,ﾊi.p.)
and its mimetic agent taltirelin hydrate (1ﾊmg/kg,ﾊi.p.), on the 3-AP-induced
change in LCGU were also investigated. The LCGU in the nuclei of the basal
ganglia, thalamus, limbic structures and brainstem of 3-AP-treated rats
was significantly lower than that of naive animals. However 3-AP increased
the LCGU of the cerebellar nuclei. TRH restored depressed LCGU in the substantia
nigra and ventral tegmental area. TRH tended to restore the lowered LCGU
in several nuclei of 3-AP-treated rats. Moreover, taltirelin further increased
the LCGU in the cerebellar nuclei. These results suggest that the motor
disturbance of the 3-AP-treated rats may be due to not only degeneration
of the olivocerebellar pathway but also dysfunction of the several areas
that play a role in motor coordination. Moreover, the anti-ataxic action
by TRH could result from metabolic restoration of the multiple motor-coordination-related
areas.
Keywords: 3-Acetylpyridine, Ataxia, Local cerebral glucose utilization,
Thyrotropin-releasing hormone,
Taltirelin hydrate