[H-3]-2-DEOXYGLUCOSE UPTAKE STUDY IN MUTANT DYSTONIC HAMSTERS - ABNORMALITIES IN DISCRETE BRAIN-REGIONS OF THE MOTOR SYSTEM

The genetically dystonic (dt(sz)) hamster, an animal model of idiopath ic paroxysmal dystonia, displays attacks of generalized twisting movem ents and abnormal postures of limbs and trunk either spontaneously or in response to mild stress. This experimental model may be helpful to give insights into the pathophysiology of idiopathic dystonia in man. In the present study, the regional uptake of [H-3]-2-deoxyglucose (2-D G) was examined in brains (75 brain regions) of dt(sz) hamsters during the expression of severe dystonia. 2-DG autoradiography revealed sign ificant changes of 2-DG uptake in discrete brain regions of dt(sz) ham sters compared with age-matched, nondystonic control hamsters. In dyst onic hamsters, a dramatic increase of 2-DG uptake was observed in the red nucleus (159% over control). Furthermore, enhanced 2-DG uptake was found in the ventromedial, ventrolateral, and anteroventral nuclei of the thalamus (19-42%) and in the medial vestibular nucleus (23%). A s ignificant decrease in 2-DG uptake in deep cerebellar nuclei (-30%) ma y be the result of decreased synaptic activity of GABAergic neurons wi thin these structures resulting in enhanced excitatory output to red n ucleus, thalamic, and vestibular nuclei. In dt(sz) hamsters, the 2-DG uptake was not significantly altered overall within the basal ganglia. Significant increases of 14% were, however, found in discrete parts o f the caudate putamen in which recent studies revealed changes of dopa mine receptors. Altered neural activity within the basal ganglia may t herefore contribute to increased 2-DG uptake in the ventral thalamic n uclei as well as to decreased 2-DG uptake (-13%) found in the reticula r thalamic nucleus. Although the present data are in line with the con cept that abnormal thalamocortical activity seems to be critically inv olved in the dystonic syndrome, altered activities in other motor area s than output structures of the basal ganglia, such as in the red nucl eus, may contribute to clinical manifestation of dystonia in mutant ha msters.