GLUTAMATE-DECARBOXYLASE (GAD67 AND GAD65) GENE-EXPRESSION IS INCREASED IN A SUBPOPULATION OF NEURONS IN THE PUTAMEN OF PARKINSONIAN MONKEYS

The cellular distribution of the mRNAs encoding for the two isoforms o f glutamate decarboxylase, GAD67 and GAD65, was analyzed by in situ hy bridization histochemistry in the caudate nucleus and putamen of contr ol and 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP)-treated park insonian squirrel monkeys. On brain sections processed with a radioact ive and a digoxigenin-labeled cRNA probe, the GAD67 and GAD65 mRNAs we re colocalized in virtually all labeled neurons of the caudate nucleus and putamen, in both control and MPTP-treated monkeys. Furthermore, n eurons labeled with the GAD cRNAs constituted at least 90% of all stri atal neurons, as estimated on adjacent Nissl-stained sections. In the two groups of monkeys, doublelabeling experiments using a combination of radioactive GAD67 or GAD65 and digoxigenin-labeled preproenkephalin (PPE) cRNA probes showed that roughly half of all neurons labeled wit h the GAD cRNAs were also labeled with the PPE cRNA probe. When compar ed to controls, GAD67 and GAD65 mRNA levels were higher in the putamen , and to a lesser extent in the caudate nucleus, of MPTP-treated monke ys. Further analysis of labeling at the cellular level in a dorsolater al sector of the putamen revealed that GAD67 and GAD65 mRNA levels in MPTP-treated monkeys were increased in PPE-labeled (presumed striato-p allidal) neurons but not in PPE-unlabeled (presumed striato-nigral) ne urons. Our results demonstrate that most neurons in the caudate nucleu s and putamen of squirrel monkeys contain the mRNAs encoding for the t wo GAD isoforms. In addition, the selective increase in GAD mRNA level s in PPE-labeled neurons provides further evidence that striato-pallid al GABAergic neurons are hyperactive in MPTP-treated parkinsonian monk eys. (C) 1997 Wiley-Liss, Inc.