Molecular Brain Research, 3 (1987) 77-82 Elsevier BRE 80015 77 Short Communications Glutamic acid decarboxylase mRNA in rat brain: regional distribution and effects of intrastriatal kainic acid Yong Sik Kim’, John W. Thomas2, Niranjala J.K. Tillakaratne3, Pascale Montpied’, Peter D. Suzdak’, Carl Banne?, Edward Ginnsl, Allan J. Tobin and Steven M. Paul’ ‘Sections on Molecular Pharmacology and Molecular Neurogenetics, Clinical Neuroscience Branch, NIMH, Bethesda, MD 20892 (USA.), 2Developmental Biology Section, Laboratory of Molecular Biology, NINCDS, Bethesda, MD 20892 (U.S.A.) and ‘Department of Biology, Molecular Biology Institute, and Brain Research Institute, University of California, Los Angeles, CA 90024 (U.S.A.) (Accepted 1 September 1987) Key words: Glutamic acid decarboxylase (GAD); Glutamine synthetase (GS); Messenger RNA (mRNA); Regional distribution; Kainic acid Glutamic acid decarboxylase (GAD) mRNA was quantified in different regions of rat brain using an antisense RNA probe (ribo- probe) prepared from a cloned feline cDNA. In all brain regions studied a single band of GAD mRNA of approximately 3.7 kb was de- tected. The level of GAD mRNA was highest in the cerebellum, followed by the hypothalamus > thalamus > striatum > hippocampus > frontal cortex = parietal cortex 3 medulla = pons. Since GAD has been previously localized to intrinsic neurons of the striatum, we examined the effects of intrastriatal kainic acid administration on striatal GAD mRNA. The level of GAD mRNA in the kainic acid- lesioned striatum was reduced by 70-75% when compared to the contralateral (unlesioned) striatum. In contrast, the level of gluta- mine synthetase (an enzyme localized to glia) mRNA was increased approximately 290% in the kainic acid-lesioned striatum. There were no significant differences in GAD mRNA levels between the ipsilateral and contralateral cerebral cortices and hippocampi of rats injected with intrastriatal kainic acid. The decarboxylation of glutamic acid by glutamic acid decarboxylase (GAD); L-glutamate carboxyl-l- lyase; EC 4.1.1.15) is the rate-limiting step in the synthesis of y-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the central nervous system. GABA has been implicated in the pathophy- siology of a number of neurological and psychiatric disorders2~“~r5. Consequently, GAD activity has been extensively measured in brain from a variety of species including man. There are, however, a num- ber of complicating factors that must be considered in quantifying GAD activity, including alternative pathways for glutamate decarboxylation and post- mortem changes in enzyme activity13. Moreover, the possible mechanisms responsible for the reported changes in GAD activity (e.g. changes in enzyme concentration, cofactor levels, etc.) in various neuro- psychiatric diseases are still unclear, although the feedback regulation of GAD activity by GABA has been proposed as one possible mechanism. Pharma- cological agents that either increase or decrease GABAergic neurotransmission have, for example, been reported to alter GAD activity8~‘4~20~25~26.29~30. With the availability of a feline cDNA probe for GAD that is homologous to human and rat GAD”, it is now possible to directly measure the levels of GAD mRNA in rat brain, and to examine the effects of neurotoxins which are known to destroy GABAergic neurons. We now report the levels of GAD mRNA in various regions of the rat brain, both before and after Correspondence: S.M. Paul, Section on Molecular Pharmacology, Clinical Neuroscience Branch, NIMH, Building 10, Room 4N214, Bethesda, MD 20892, U.S.A. 0169-328X/87/$03.50 0 1987 Elsevier Science Publishers B.V. (Biomedical Division)