Screening Of Differentially Expressed Genes In Adult Rats Dopamine-depleted Striatum And Proteomics Research On CSF Of Parkinson's Disease

Parkinson' s disease (PD)is a commonly seen neurodegenerative disorders, and its incidence is about 1% in over 55-year aged people. Its main pathological changes is progressive denature and loss of dopaminergic neurons in substantia nigra pars compacta, giving rise to dysfunction of nigrostriatal dopaminergic pathway, then appearance of abnormal movements, such as rigidity, tremor. The pathological mechanism of PD is very complicated, up to now, it has explored that DA neurodegeneration may be resulted from many complicated molecular mechanisms, such as mitochondrial dysfunction, oxidative stress, environmental toxin, genetic factors, cell apoptosis, excitatory toxin and auto-immoune. Due to limited knowledge in key molecular pathological PD, the therapeutic measurements mainly focus on syndromes. How to protect the remaining DA neurons become the most important strategy for PD. The previous researchs showed once the brain was damaged the targeted-area cells of the injuried regions would secret protective factors, such as up-regulation of neurotrophic factors and growth factors which will play great role in survival of remaining neurons, synapse forming and rebuilding of neuronal circle, and may activate the precusor cell, promote proliferation, differentiation and repair. Striatum is the projective target of DA neurons, but there has few reports on gene changes during PD pathogensis. Objective:To further explore pathogensis of PD through large-scale screening differentially expressed genes in adult rats dopamine-depleted striatum.Methods:Thirteen healthy adult female SD rats were randomly divided into experimental anf control groups. Dopamin- depleted PD model was induced by 6-OHDA and tested by apomorphine. Five weeks later, total RNA of striatum of the rats were extracted, then the differentally expressed genes were screened out by gene chip, funrthermore, a set of interested genes confirmed by RT-PCR analyse.Results:Totally, 61 differentially exprssed genes were screened out from dopamine-depleted striatum of PD rats induced by 6-OHDA by gene chip, these differentially expressed genes mainly were grouped into cytosketal protein, metabolism enzymes, iron-channel protein, adhensive molecules, receptors promoting survival and inducing apoptosis, signal transduction molecules and ribosome protein involving in protein synthesis.Conclusion:Complicated molecular events generated in striatum following 6-OHDA damage, which revealed that a seried reactions involve in degeneration and die of DA neuron.