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Cerebellar excitatory and inhibitory amino acid receptors in multiple system atrophy

Department of Neurology (R. Price and Drs. Penney and Young), Massachusetts General Hospital, Boston, MA; the Department of Neurology (Drs. Albin and Sakurai), University of Michigan, Ann Arbor, MI; and the Neuropharmacology Section (Dr. Polinsky), National Institute of Neurological Disorders and Stroke, Bethesda, MD.

We studied excitatory and inhibitory amino acid binding sites autoradiographically in control and multiple system atrophy (MSA) cerebella. Within the dentate nucleus (DN) of MSA specimens, we found a significant increase in the level of GABA_A, benzodiazepine, and metabotropic binding sites compared with controls. In the granule cell layer, kainate, JV-methyl-D-aspartate, and GABA_A binding sites were all decreased significantly in MSA specimens compared with controls. In the molecular layer of MSA cerebellum, a-amino-3-hydroxy-5-methylisoxazole-4-propionate binding sites were decreased significantly compared with controls. Cerebellar cortical binding site decreases are likely due to Purkinje and granule cell loss. The increase of binding site levels in DN of MSA specimens may represent receptor up-regulation reflecting loss of descending inhibitory Purkinje cell and ascending excitatory afferents to the DN.

Address correspondence and reprint requests to Dr. Anne B. Young, Neurology Service, Massachusetts General Hospital, Fruit Street, Boston, MA 02114.

Supported by USPHS grants NS01300, NS19613, NS15655, and AG08671.

Received September 21, 1992. Accepted for publication in final form December 1, 1992.

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