Jpn. J. Pharmacol. 72 (3), 241-246 (1996)

Alterations in Local Cerebral Glucose Metabolism and Endogenous Thyrotropin-Releasing Hormone Levels in Rolling Mouse Nagoya and Effect of Thyrotropin-Releasing Hormone Tartrate

Takahiro Nakayama and Yasuo Nagai

Pharmaceutical Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., 17-85 Juso-honmachi 2-chome, Yodogawa-ku, Osaka 532, Japan

Abstract: To identify the brain region(s) responsible for the expression of ataxic gaits in an ataxic mutant mouse model, Rolling mouse Nagoya (RMN), changes in local cerebral glucose metabolism in various brain regions and the effect of thyrotropin-releasing hormone tartrate (TRH-T), together with alterations in endogenous thyrotropin-releasing hormone (TRH) levels in the brains of RMN, were investigated. Ataxic mice [RMN (rol/rol)] showed significant decreases in glucose metabolism in regions of the diencephalon: thalamic dorsomedial nucleus, lateral geniculate body and superior colliculus; brain stem: substantia nigra, raphe nucleus and vestibular nucleus; and cerebellar nucleus as compared with normal controls [RMN (+/+)]. When RMN (rol/rol) was treated with TRH-T (10 mg/kg, equivalent to 7 mg/kg free TRH), glucose metabolism was significantly increased in these regions. These results suggest that these regions may be responsible for ataxia. We also found that TRH levels in the cerebellum and brain stem of RMN (rol/rol) were significantly higher than those of RMN (+/+). These results suggest that ataxic symptoms in RMN (rol/rol) may relate to the abnormal metabolism of TRH and energy metabolism in the cerebellum and/or brain stem and that exogenously given TRH normalizes them.

Keywords: Thyrotropin-releasing hormone tartrate, Local cerebral glucose metabolism, Rolling mouse Nagoya

Copyright© The Japanese Pharmacological Society 1996

[Back to TOC]