Neurochemical analysis on a brain of pure pallidal degeneration with special reference to the termination of GABA ergic pallido-thalamic tract in the thalamus

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1) Neurotransmitter markers were measured in brain regions of a very rare case of pure pallidal degeneration (PPD) as compared with 16 controls. Gamma-aminobutylate (GABA) concentration was remarkably decreased in extemal (GPe) and internal (GPi) pallidum (GP) and subthalamic nucleus (ST), glutamate concentration was increased markedly in GPi and ST, and choline acetyltransferase (CHAT) activities in GP, ST, ventroanterior (VA) and ventrolateral (VL) nucleus of the thalamus. Noradrenaline concentration in GP was decreased moderately. Dopaminergic and serotonergic systems showed no remarkable change in all the regions examined. These results suggest that the changes of neurotransmitter markers reflect selective degeneration of GP neurons and their efferent fibers, and also of terminals of striatopallidal GABAergic fibers and probably noradrenergic fibers within GP. Because ChAT activities were increased only in GP and its terminal areas, increase of ChAT activity might be a representation of a compensatory reaction against GP neuronal damage in PPD brain. These sets of neurochemical changes are the pathophysiological basis of the characteristic slow movement in PPD patient. 2) Using microdissection method, fine distribution of GABA in the thalamus was analyzed in PPD and 4 control brains. GABA concentration was specifically decreased in PPD brain in the ventro-oral nucleus of VL, which indicates that pallidothalamic fibers contain GABA as a neurotransmitter in the human brain and terminate in the very restricted area of VL thalamus.