| BackgroundParkinson’s disease (PD) is a common neurodegenerative disease in the elderly. The PD’s pathogenesis is very complex, and there is no precise targeted treatment. At present, the treatment of PD mainly alleviate symptoms and improve the patient’s quality of life. A large number of researches show that the glial cell line-derived neurotrophic factor has a protective effect on brain neurons. However, it is has not been reported at home and abroad, the distribution and variation of glial cell line-derived neurotrophic factor(GDNF), neurturin(NTN), persephin (PSP) in PD rat model’s substantia nigra and the striatum on different time points, as well as on the basis of application of minocycline.Objective1To understand the distribution and variation of GDNF, NTN, PSP in PD rat model’s substantia nigra and the striatum on different time points to reveal the relevance of the GDNF family and the PD.2Application of minocycline role in the PD rat model, to further understand the change of GDNF, NTN, PSP on different time points, in order to explore the protective effects of minocycline on PD.Method1Using the6-OHDA stereotaxically injected in rat striatum and substantia nigra to selectively damage the dopamine (DA) neurons in substantia nigra, resulting in a rat model of PD. On this basis, given minocycline intragastric administration to prepare the minocycline group of model.2Using the subcutaneous injection of Apo morphine (0.05mg/kg) induced the rotation behavior to evaluate if the PD model successful. Application of mNSS scoring scale to ccomprehensively evaluate the changes of rat movement, sensation, reflection and balance function.3Using the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) to detect the expression of GDNF mRNA, NTN mRNA, PSP mRNA in substantia nigra and striatum respectively of all model rats. To discuss the distribution and variation of GDNF, NTN, PSP in substantia nigra and striatum of rats model on different time points and the protective effects of minocycline on PD.Result1The shows of behavior detectionThere is no obviously change between the blank group and the sham operation group, the mNSS ratings are0. The typical PD symptom like tremor, rigidity, slow movement appeared on the model group and the minocycline group, there are also symptoms of piloerection and arched. The model group’s mNSS score are mostly between13to18, it belongs to the severe damage. The minocycline group’s mNSS score are mostly between7to12, it belongs to the moderate damage.2The shows of semi-quantitative RT-PCR analysis2.1The result of GDNF mRNA in the substantia nigra and striatum(1)From the same time point:The level of GDNF mRNA in the PD rat group substantia nigra and striatum was lower than the blank group and the sham operation group. The difference was statistically significant (P<0.05). Compared with the PD group, the level of GDNF mRNA in the minocycline group increased, the difference was statistically significant (P<0.05).(2)From the different time point:The GDNF mRNA expression of the PD group had a continuous decreasing trend in a time-dependent manner, but the difference was not statistical significant (P>0.05) at all time points. The GDNF mRNA expression of the minocycline group was in a continuous increasing trend. 2.2The result of PSP mRNA in the substantia nigra and striatum(1)From the same time point:The levels of PSP mRNA between group N and group F were no significant difference (P>0.05). The levels of PSP mRNA in substantia nigra and striatum of PD group were lower than the blank group and the sham operation group (P <0.05). The difference was statistically significant. Compared with the PD group, the level of PSP mRNA of minocycline group was higher (P<0.05), which was statistically significant.(2)From the different time point:the levels of PSP mRNA reached to the lowest peak at the24h.2.3The result of NTN mRNA in the substantia nigra and striatum(1)From the same time point:The levels of NTN mRNA in substantia nigra and striatum of PD group were lower than the blank group and the sham operation group(P<0.05). The difference was statistically significant. Compared with the PD group, the level of NTN mRNA of minocycline group was higher (P<0.05),,which was statistically significant.(2)From the different time point:with time prolonging, the NTN mRNA expression of the PD group was in a continuous decreasing trend. The NTN mRNA expression of the minocycline group was in a continuous increasing trend, and reached to the lowest peak on the14h.Conclusion(1) The relative expression quantity of the PD group’s GDNF mRNA, NTN mRNA, PSP mRNA decreased with time prolonging.(2) The minocycline can reduce the rat’s behavior detection of PD.(3)The minocycline can increase the relative expression quantity of GDNF mRNA, NTN mRNA, PSP mRNA. It also can protect primary dopaminergic neurons by inhibiting the glial cells release cytokines and chemokines. |
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