NMDA NR1 subunit mRNA and glutamate NMDA-sensitive binding are differentially affected in the striatum and pre-frontal cortex of Parkinson's disease patients

Changes in the levels of mRNA for the NR1 subunit of the glutamate NMDA rec eptor and in NMDA-sensitive glutamate binding were investigated in consecut ive sections of the prefrontal cortex and striatum of control and Parkinson 's disease (PD) post-mortem brain using in-situ hybridisation and receptor autoradiography. Both markers of NMDA receptors were found to be relatively unaffected when measured by microdensitometry in the prefrontal cortex of control and PD brains. At a cellular level, a subpopulation of small and me dium neurons in the superficial layers of the prefrontal cortex of the PD g roup showed a decreased expression of NMDA NR1 mRNA, with the maximal decre ase in cortical layer IV. In the striatum, levels of glutamate binding to t he NMDA receptor detected by receptor autoradiodgraphy were significantly r educed in the PD group, while no change could be detected at a macroscopica l level in NMDA NR1 mRNA expression. Consequently, we suggest that the impo rtant decrease in agonist binding to the NMDA receptor observed in this stu dy in the caudate and putamen of PD brains, in the absence of any major cha nge in NMDA NR1 mRNA levels might reflect the degeneration of pre-synaptic NMDA receptors located on nigro-striatal projections particularly affected by the disease. Small changes observed at a cellular level in subsets of ne urons of both prefrontal cortex and striatum will be discussed at the light of neurochemical changes characteristics of PD. (C) 1999 Elsevier Science Ltd. All rights reserved.