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Brain and Nerve No to Shinkei Volume 37, Issue 12 （December 1985）

Brain and Nerve 脳と神経 37巻12号（1985年12月発行）

Japanese English

原著

TRH （thyrotropin-releasing hormone）のマウス，ラット脳内GABA （γ—aminobutyric acid）代謝に及ぼす効果について—GAD （glutamic acid decarboxylase），GABA-T （GABA transaminase）活性およびGABA再取込みでの検討 EFFECT OF THYROTROPIN RELEASING HORMONE (TRH) ON GABA (GAMMA AMINOBUTYRIC ACID) METABOLISM IN MOUSE AND RAT BRAINS:AS TO THE ACTIVITIES OF GAD (GLUTAMIC ACID DECARBOXYLASE),GABA-T (GABA-TRANSAMINASE) AND GABA RE-UPTAKE 倉橋幸造 ¹ , 兼子直 ² , 松永宗雄 ³ , 佐藤時治郎 ² , 武部和夫 ¹ Kozo Kurahashi ¹ , Sunao Kaneko ² , Muneo Matsunaga ³ , Tokijiro Sato ² , Kazuo Takebe ¹ ¹弘前大学医学部第三内科 ²弘前大学医学部精神神経科 ³弘前大学医学部脳研神経内科 ¹Third Department of Internal Medicine, Hirosaki University School Mredicine ²Department of Neuropsychiatry,Hirosaki University School of Medicine ³Department of Neurology,CVD Research Institute, Hirosaki University School of Medicine pp.1211-1216

発行日 1985年12月1日 Published Date 1985/12/1

DOI https://doi.org/10.11477/mf.1406205632

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Abstract 文献概要
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　抄録　TRH （thyrotropin releasing hormone）は幾つかの神経疾患に対して臨床応用されている神経ペプチドである。TRHの中枢性効果はモノアミンを初めAch （acetylcholine）系，GABA （γ—aminobutyric acid）系等との密接な相互作用に基づくものと想定されているが，詳細は不明である。そこでGABA系のうち今まで検討されていなかった代謝的側面に対するTRHの影響をマウス，ラットを用いて検討した。指標にはGABA合成酵素GAD （glutamic acid decarboxytase）および分解酵素GABA-T （GABA-transaminase）活性と大脳皮質，小脳切片での［³H］GABA再取込みを選んだ。ddマウスのGAD,GABA-Tは5 mg／kgのTRH腹腔投与60分後に前脳では不変，後脳では増加傾向をみた。GADは脳幹で増加（p＜0.001，小脳では逆に低下（p＜0.05）していた。GABA取込みはWistar雄ラットで検討したが，TRH （0.1mM—0.1μM）はGABA取り込みを変化させなかった。GAD活性に対するTRHの効果はラットでは脳の7部位で検討し，投与30分後の視床一中脳（p＜0.05）と180分後の橋一延髄（p＜0.05）でGAD活性の増加が示されたが，他部位は不変であった。この結果よりTRHの中枢作用を考える際，GABA系の関与が無視しえないものと考えられた。

It has been reported that thyrotropin-releasing hormone (TRH) improves the ataxia of cerebellar type. The mechanism of action is unclear. As well recognized, GABA (gamma aminobutyric acid) is an important neurotransmitter in cerebellar sys-tem. So, if TRH acts on cerebellum, it is expected that the GABA metabolism will be modified by in vivo or in vitro TRH application. The purpose of this experiment is to clarify whether or not TRH affects on GABA system in cerebellar sys-tem.

The first experiment was to determine the effect of TRH on the two GABA related enzyme activi-ties, that is, GAD (glutamic acid decarboxylase) and GABA-T (GABA-transaminase). TRH was intraperitoneally injected at a dose of 5 mg/kg. In mouse brains, the two enzyme activities of hindbrains increased after 60 minutes. Next ex-periment assaying GAD activities at two parts of hindbrain revealed that the increase in hind-brain observed above was due to marked increase in brain-stem (p <0.001), but not in cerebellum itself in which the GAD activities decreased (p< 0.05). On the other hand, in the forebrains, the same dose of TRH failed to change both GAD and GABA-T activities. In order to ascertain the effect more precisely, we assayed GAD activities at seven parts of the brain of Wistar male rats. By this experiment, it was found that GAD acti-vities increase at two portions, namely, at thala-mo-midbrain after 30 minutes and at pons-medulla after 180 minutes of TRH injection (p<0.05, in both). Other five portions, including cerebellum, showed no significant change of GAD activities.

The second experiment was to examine the in vitro effect of TRH on GABA re-uptake, using the slices of cerebral cortex or cerebellum. Underthe concentrations from O.1 mM to 0.1 μM, TRH failed to show any significant change of GABA re-uptake when compared to control.

These results indicate that TRH can modify central GABAergic system. Furthermore, mainmetabolic changes do not occur in cerebellum itself, but in adjacent portions, intimately related with cerebellar system, such as pons-medulla or mid-brain-thalamus.