| Background and ObjectiveParkinson’s disease(PD) is the second largest disorder of neurological degeneration, which affects approximately fifty million people in the world. Of the older cohort aged over 65, the morbidity up to one point sevent percent in China is obviously higher than one percent in Western country. It’s well known that aging is the key risk factor for PD. As our country has stepped into the senile society, PD has become to be one of disorders which severely harmed people’s health. So it is necessary for us to perform the prevention and treatment to decrease the occurrence of PD. The chronic progressive degeneration and loss of substantia nigra dopamine neurons are the basis of pathogenesis. Nevertheless, the present treatments involving replacement therapy with dopamine(DA) and the application of DA receptor agonist that are not capable of stopping the progressive death of neurons and slowing the progress of PD, can just remit clinical symptoms. Therefore, exploring new cured strategy and seeking effective neural protective target for PD patients is becoming more necessary.Curcumin is one kind of phenol pigment, which is the important active component of turmeric, characterized by anti-inflammation and anti-oxidative stress. Rotenone can make functional deficiency of respiratory chain and disorder of energy generation by penetrating blood-brain barrier and inhibiting activity of mitochondrial complex I. As a result, a series of the above-mentioned reactions can break balance of internal environment, can induce lipid peroxidation and tremendous free radicals come into being, finally leading to cell apoptosis and degeneration and loss of dopamine neurons. The process of generation and progress of PD can be established and modeled by subcutaneous injection of low-dose rotenone. Additionally, the changes of throsine hydroxylase(TH) at midbrain substantia nigra area to some extent represent function status of DA neurons.Insulin-like growth factor 1(IGF-1) is one of non-selective neurotrophic factors, which can exert protective effect on both in vitro and in vivo. Protein kinase B(PKB, named Akt) is the key factor for mediated cell survival by some approaches. FoxO3a regarded as homologous protein of transcription factor O sub-family, has become to be hot topic all over the world as it can regulate and control nerve cell cycle and apoptosis. When Akt path is inhibited, FoxO3a dephosphorylates, after that, which over-expresses in the cell nuclear and regulates different apoptosis target to make cells death. The mechanism that neuron apoptosis is reduced after activation of PI3K-Akt path, FoxO3a dephosphorylation, decrease of nuclear expressions, indicates that FoxO3a dephosphorylation is regulated by PI3K-Akt path. IGF-1 is upstream regulatory factor of the signal path. After the DA-neural degeneration induced by rotenone, how the TH changes and what change the relative molecules referring to cell apoptosis path have still remains unclear. It is not clear whether the protection function of curcumin for DA-neurons is accomplished through changing IGF-1/Akt/FoxO3a signal path to regulate cell apoptosis.In our trial, the mRNA and protein expression of TH and the expressions of IGF-1, phosphorylated-Akt(p-Akt) and phosphorylated-FoxO3a(p-FoxO3a) were examined in samples of substantia nigia, in order to explore potential mechanism that curcumin has an protective effort on DA-neurons in rotenone-induced PD rats and provide theoretical basis for the future application of curcumin in the prevention and treatment of neurodegenerative diseases. Materials and MethodsSPF(specific pathogen free) male SD rats were selected and randomly divided into blank group, control group(curcumin group), model group(rotenone group) and treatment group, twenty rats in each group. The back and neck of rats in blank group and control group were subcutaneously injected with sunflower oil, while the rest were injected with rotenone continuously for 28 days. After models were successfully established, the changes of behavioristics were calculated and assessed. Then the control group and treatment group received curcumin by gastric perfusion, and the remaining groups were administrated equivalent dimethyl sulfoxide in the same way for 28 days. At last, all rats were killed.In-situ hybridization and western blotting were used for detection of expressions of IGF-1, p-Akt and p-FoxO3a. Furthermore, the mRNA and protein expression of TH were tested by RT-PCR and immunohistochemical staining method. ResultsThe expression of TH protein: Average optical density of TH positive neurons were occurred in both the blank group and the control group, which were decreased in the model group. In a word, the treatment group showed higher expression level compared with the model group, and showed lower expression level than the blank and control groups, with statistically significant differences(P<0.05).The expression of TH mRNA: Relative expression of TH mRNA were occurred in both the blank group and the control group, which were decreased in the model group. In a word, the treatment group showed higher expression level compared with the model group, and showed lower expression level than the blank and control groups, with statistically significant differences(P<0.05).The expressions of IGF-1, p-Akt and p-FoxO3a proteins: The protein expressions of IGF-1, p-Akt and p-FoxO3a were occurred in the blank group and the control group, which were decreasingly expressed in the model group. what’s more, the expression levels in the treatment group were significantly higher than that in the model group, and were obviously lower than that in the blank and control groups(P<0.05). ConclusionsLow-dose rotenone administrated by subcutaneous injection can be applied to establish successful chronic PD rat model.The dopamine neurons at substantia nigra area of PD rats are apparent loss. Curcumin potentially alleviates the drops via up-regulating the expressions of IGF-1.Cell apoptosis may be increased when the apoptosis path is activated in PD rats. Probably, curcumin can inhibit the process through activating Akt/FoxO3a path to mediate cell survival.Based on the regulation of Akt/FoxO3a signal path, curtimin has beneficial effects on reducing cell apoptosis and decreasing the loss of dopamine neurons. |
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