The Relationship Of Astrocytes Activation Stimulated By LPS And Degeneration Of Dopaminergic Neurons In Substantia Nigra In Rats

Aim: To investigate the effects of activated astrocytes induced by lipoplysaccharide(LPS) on the degeneration of dopamine neurons in substantia nigra (SN).Methods: LPS was stereotaxically injected into substantia nigra. At different survival times after injection, the glial fibrillary acidic protein(GFAP) of astroglia, the tyrosine hydroxylase(TH) of dopamine neurons and heme oxygenase-1 were observed by immunohistochemical staining, reduced glutathione(GSH) was observed by colorimetric method, and the level of glutamate and gamma-aminobutyric acid in the striatum corpora was measured by microdialysis and high performance liquid chromatography with electrochemical detection(HPLC-ECD).Results: 6h after injection of 10μg LPS into the rat SN, GFAP-positive astrocytes and HO-1 began to be activated. At the 2nd week post-injection GFAP-positive astrocytes and HO-1 reachμed to peak( GFAP+ cells:124.83±19.09,HO-1+ cells:89.17±9.89), and at the 4th week the number of GFAP-positive astrocytes and HO-1 began to decrease. There are significant deviation between the groups of post-injection and the control groups (P<0.05). Compared with the control groups, the number of TH positive neurons and GSH began to decrease on the 2nd week after injection, and reached a lowest level on the 4th week (TH+ cells:25.50±19.73,GSH:14.40±3.10). Compared with the control groups, all the groups excepted for 6h performed a significant decrease (P<0.05).The level of the Glu and GABA of striatum began to increase on the 4th week after LPS injection ( Glu: 21.48±3.37,GABA:1.88±0.22,Compared with the control group P<0.01). The level of GABA reached the highest level on the 6th group(1.94±0.41).Conclusion: LPS-induced astrocytes activation precedes dopaminergic neuron degeneration. Activated astrocytes play important role in the inflammation of SN, which...