Subthalamic nucleus lesions are neuroprotective against terminal 6-OHDA-induced striatal lesions and restore postural balancing reactions

Inactivation of the subthalamic nucleus (STN) by deep brain stimulation or lesioning can ameliorate symptoms in Parkinson' disease (PD) and may alter the underlying progressive degenerative process. We evaluated the effects o f STN lesions in a terminal lesion model of Pl) in rats. Multiple intrastri atal 6-ODHA injections (4 X 7 mug) resulted in a partial loss of striatal T H-positive innervation (-30 to -40%) and nigral dopaminergic neurons (-60%) , which was associated with behavioral deficits as observed in drug-induced rotational asymmetry, side-stepping, and postural balancing reactions. Uni lateral ibotenic acid lesions of the STN did produce a 50-60% loss of STN n eurons based on stereological analysis, which did not induce a functional i mpairment in rotational asymmetry or spontaneous sensorimotor behaviors. Wh en STN lesions were performed 1 week prior to the 6-OHDA terminal striatal lesions, a significant rescue effect (+23%) on nigral dopaminergic neurons against terminal 6-OHDA neurotoxicity could be demonstrated, whereas striat al TH-positive fiber loss was not attenuated in these animals. In addition, animals with combined STN and striatal lesions exhibited a significant rec overy in postural balancing reactions induced by 6-OHDA terminal lesions an d did not show a significant impairment in any of the other behavioral para meters examined. Taken together, STN lesions can exert neuroprotective effe cts on nigral dopamine neurons in a partial lesion model of Pl) which resul t in recovery of spontaneous sensorimotor behavior. These findings may ther efore provide new insights into the functional interaction between the glut amatergic and the dopaminergic neurotransmitter systems and foster novel th erapeutic concepts for the early and middle phases of Parkinson's disease. (C) 2001 Academic Press.