促甲状腺激素释放激素及其类似物TA-0910通过腹侧被盖区代谢正常化对滚动小鼠名古屋品系的抗共济失调作用。

Anti-ataxic effects of TRH and its analogue, TA-0910, in Rolling mouse Nagoya by metabolic normalization of the ventral tegmental area.

Kinoshita K, Watanabe Y, Asai H, Yamamura M, Matsuoka Y

Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd, Saitama, Japan.

Br J Pharmacol. 1995 Dec;116(8):3274-8. doi: 10.1111/j.1476-5381.1995.tb15135.x.

The mechanism of the anti-ataxic action of thyrotropin-releasing hormone (TRH) and its analogue. TA-0910, in the Rolling mouse Nagoya (RMN), an ataxic mutant mouse, has been investigated. 2. TRH (30 mg kg-1, i.p.) and TA-0910 (3 mg kg-1, i.p.) reduced the fall index (number of falls/spontaneous motor activity), an index of ataxia, 10-30 and 10-60 min after administration, respectively. 3. Relative local cerebral glucose utilization (LCGU) in the cerebellum and ventral tegmental area (VTA) of the rolling mouse was significantly smaller than that in normal animals. TRH (30 mg kg-1, i.p.) and TA-0910 (3 mg kg-1, i.p.) increased the relative LCGU value of the VTA but not of the cerebellum in rolling mice to the level of normal animals. 4. These results suggest that the ataxia of the rolling mouse may be due to dysfunction of the cerebellum and VTA, and that amelioration by TRH and TA-0910 could result from metabolic normalization of the VTA.

促甲状腺激素释放激素（TRH）及其类似物TA - 0910对滚动小鼠名古屋品系（RMN）这一遗传性共济失调突变小鼠的抗共济失调作用机制已得到研究。2. TRH（30毫克/千克，腹腔注射）和TA - 0910（3毫克/千克，腹腔注射）分别在给药后10 - 30分钟和10 - 60分钟降低了共济失调指数（跌倒次数/自发运动活动）。3. 滚动小鼠小脑和腹侧被盖区（VTA）的相对局部脑葡萄糖利用率（LCGU）显著低于正常动物。TRH（30毫克/千克，腹腔注射）和TA - 0910（3毫克/千克，腹腔注射）使滚动小鼠VTA的相对LCGU值升高至正常动物水平，但小脑的未升高。4. 这些结果表明，滚动小鼠的共济失调可能是由于小脑和VTA功能障碍所致，而TRH和TA - 0910的改善作用可能源于VTA代谢的正常化。

Anti-ataxic effects of TRH and its analogue, TA-0910, in Rolling mouse Nagoya by metabolic normalization of the ventral tegmental area.