Experimental study on protection of extrogeneous kynurenic acid on rat nigral dopamine neurons

Objective To verify and evaluate the protective function of glutamine (Glu) receptor antagonist , kynurenic acid(KYNA), on the dopaminergic(DA) cell bodies and fibres of substantia nigra pars compacta. Methods A total of 40 adult female SD rats in 4 groups (each of 4 groups consisting of 10 rats), GroupA, B, C, D received, respectively , an unilateral microinjection of normal saline, KYNA, KYNA + 6 OHDA , which was microinjected thirty minutes prior to 6 hydroxydo pamine (6 OHDA),or 6 OHDA, into the left ventral tegmental area and substantia nigra pars compacta. Two weeks later, the change of tyrosine hydroxylase (TH) positive neurons in substantia nigra pars compacta and dopaminergic fiber in ventral tegmental area were investigated in immunocytochemical methods.Results In the third day after injection, the ethologic observation was performed following motivation by apomorphine. Group A and B had no symptom. Group C was significantly improved compared with group D. The number of TH positive cells in group A, B, C significantly increased in comparison with the group D( P 0.01). Application of KYNA prior to 6 OHDA produced more significant increase of TH positive fiberic density than group D around the injection sites in ventral tegmental area . Conclusion These data indicate that the early application of Glu receptor antagonist KYNA may decrease neurotoxic damage of 6 OHDA on nigral DA neurons.