In Situ Hybridization Studies of Glutamic Acid Decarboxylase Gene Expression in Post‐mortem Cerebral Cortex in Parkinson's Disease

Parkinson's disease (PD) patients suffer from motor disorders but mild to severe cognitive deficits can also be present. The dorsolateral prefrontal cortex (DLPFC) is associated with cognitive deficits in PD and alterations in muscimol binding in DLPFC Brodmann area 9 (BA9) have been reported in PD patients (Nishino et al., 1988). In order to further assess the possibility that GABAergic activity is altered in PD patients, gene expression of the GABA‐synthesizing enzyme, glutamic acid decarboxylase (GAD67), was examined in BA9 in post‐mortem brains using isotopic in situ hybridization histochemistry on X‐ray films and emulsion radioautographs. In brains from PD patients, we show that GAD67 mRNA labeling is significantly decreased compared to control cases, and this decrease is detected in patients with and without dementia. This supports the possibility that GABAergic neurotransmission is deficient in the DLPFC in PD. We speculate that this impairment is involved in some of the cognitive deficits associated with the disease. This work is supported by the American Parkinson's Disease Association.