The isomers of thioctic acid alter 14C-deoxyglucose incorporation in rat basal ganglia

Abstract

Nigral cell death in Parkinson's disease is associated with decreased reduced glutathione (GSH) levels, impaired complex I activity and inhibition of α-ketoglutarate dehydrogenase (α-KGDH) in substantia nigra. Thioctic acid exerts antioxidant activity through a thiol-disulphide redox couple and is an essential cofactor for α-KGDH. However, it is not known whether or not thioctic acid enters basal ganglia or exerts beneficial effects in Parkinson's disease. As a global measure of altered cerebral function, the effect of R- and S-thioctic acid on 14C-2-deoxyglucose ( 14C-2DG) incorporation was investigated in rats. Rats were treated with either R- or S-thioctic acid (50 mg/kg IP) or 0.9% saline acutely or for 5 days and 14C-2DG incorporation in basal ganglia was assessed. Following acute administration, R- but not S-thioctic acid caused an overall increase in 14C-2DG incorporation that was significant in both substantia nigra zona compacta and zona reticulata. R-thioctic acid also increased the incorporation of 14C-2DG in the medial forebrain bundle, thalamus, and red nucleus. S-thioctic acid decreased 14C-2DG incorporation in the subthalamic nucleus, but increased it in the red nucleus. Following repeated administration, R-thioctic acid no longer increased 14C-2DG incorporation in either zona compacta or zona reticulata of substantia nigra. However, both R- and S-thioctic acid now decreased 14C-2DG incorporation in the subthalamic nucleus. The data suggest that thioctic acid does enter the brain and can alter neuronal activity in areas of the basal ganglia intimately associated with the motor deficits exhibited in Parkinson's disease.