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Effect of trh on gamma aminobutyric acid metabolism in mouse and rat brains as to the activities of glutamic acid decarboxylase gamma aminobutyric acid transaminase and gamma aminobutyric acid re uptake



Effect of trh on gamma aminobutyric acid metabolism in mouse and rat brains as to the activities of glutamic acid decarboxylase gamma aminobutyric acid transaminase and gamma aminobutyric acid re uptake



Brain & Nerve 37(12): 1211-1216



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 aminobutryic acid) is an important neurotransmitter in cerebellar system. 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 system. The first experiment was to determine the effect of TRH on the two GABA related enzyme activities, 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 experiment assaying GAD activities at two parts of hindbrain revealed that the increase in hindbrain 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 activities increase at two portions, namely, at thalamo-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. Under the concentrations from 0.1 mM to 0.1 .mu.M, 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, main metabolic changes do not occur in cerebellum itself, but in adjacent portions, intimately related with cerebellar system, such as pons-medulla or midbrain-thalamus.

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