Neuroprotective Effects Of GDNF On Doaminergic Neurons Of The Substatia Nigra In Rat Parkinson's Disease Model Induced With 6-Hydroxydopamine

To investigate the neuroprotective effects of different dose of the glial cell line-derived neurotrophic factor (GDNF) on the dopaminergic neurons, hemiparkinson's disease(PD) rat models were induced with the 6-hydroxydopamine(6-OHDA) injected into unilateral intramedial forebrain bundle(MFB). The numbers and morphology of dopaminergic neurons, microglias and astrocytes were examined by imrnunohistochemistry in the substatia nigra (SN) of all animals at the 3rd, 7th and 14th day following 6-OHDA injections.The animals following 6-OHDA injection were treated with the different doses of human recombinant GDNF (10μg,100μ g ) into the ipsilateral striatum simultaneously. After 4 weeks' treatment,only the dopaminergic neurons were examined in the SN of these animals.Results:1 .TH-immunoreactive(IR) positive cells were located mainly in the SN par compacta(SNpc),being scattled in the pars lateralis and reticulata. These cells were fusiform,trigonal or elongated and arranged in layers.In the groups treated with the 6-OHDA,the morphologic of TH positive cells were not found obvious changes , the number of TH-IR positive cells decreased gradually from the 3rd day,and the grey mean of lesioned SN increased,compared with the noninjected side.At the 7th day,the number ofit decreased obviously,and we can see a few cells remainning at the 14th day.Prior to injection ,the occurrence of microglias was higher in the SN than in other areas by CD68 immunohistochemistry.We found an increased staining with CD68-IR in the ipsilateral SNpc.The staining density became stronger.Some microglias became hypertrophic with the larger round cell bodies and the processes of activated microglia became more shorter and thicker.Compared with the noninjected side,the number of CD68-IR cells increased from the 3rd day and the grey mean began to decrease.The number of CD68-IR cells increased obviously at the 7th day and singnificantly at the 14th day.The activated astrocytes of lesioned side became hyperthophic with the strongly stained round cell bodies and with shorter and thicker processes.As the number of TH-IR cells decreased,the number of astrocytes increased and the grey mean of it began to decline.2. In the control groups only treated with the 6-OHDA,the number of the TH-IR cells in the SN of the lesioned side decreased significantly to 8.75 ± 1.54 % compared with the controlateral SN. The TH-IR positive neurons in the SN were greater in number of animals receiving 10 or 100 u g of GDNF than those receiving saline with anti-TH immunohistochemistry.In the groups treated with 10 u g of GDNF,the number of TH-IR cells was 58.13 + 10.10 %. In the groups treated with 100 u g of GDNF,the number of TH-IR cells was 82.78+10.51 %. These results also had shown that the neuroproctive of 100 u g of GDNF was more potent than that of 10 u g of GDNF.Conclusion: The PD animal model could be made successfully by injection of 6-OHDA into the MFB. The morphological results indicate that direct delivery of the GDNF into the striatum after 6-OHDA lesioning could induce prominent neuroprotective effects on the dopaminergic neurons. The effects of GDNF were dose-dependent.