Alterations of the distribution and of the subunit composition of the N-methyl-D-aspartate receptors in the basal ganglia of the parkinsonian rat

The loss of the dopamine-containing neurons of the substantia nigra, the major hallmark of Parkinson's disease, leads to many 'knock-on' effects in the brain, which include both structural and chemical changes. Alterations in brain cells that communicate using the excitatory substance, glutamate, to communicate with other brain cells, may in part underlie the symptoms of Parkinson's disease. The effects of glutamate are mediated through a group of molecules referred to as 'glutamate receptors' and alterations in these molecules have been identified in Parkinson's disease. The object of this project is to determine precisely where the changes in glutamate receptors occur in a model of the disease by using an electron microscope. We will thus provide essential information about glutamate receptor properties and function, and information about site of action of drugs, with the aim to define new therapeutic strategies for the treatment of Parkinson's disease.