DEPARTMENT OF ANIMAL PHYSIOLOGY

Parkinson's disease (PD) has long been characterised as a movement disorder. The cause of PD is unknown. Currently, the diagnosis of PD is based on its characteristic motor dysfunction, which first occurs when most dopaminergic neurons in the Substantia nigra (SN) are already degenerated. There are no treatments that could stop or slow down the neurodegenerative process. The motor dysfunction can only be compensated symptomatically by dopamine replacement or dopamine receptor agonists for a limited time. However, the symptomatology of PD is more heterogeneous, with significant non-motor symptoms long before the onset of the classical motor dysfunction. This premotor phase can be characterised by olfactory dysfunction, anxiety, cognitive impairment, and constipation. Its pathogenic process is presumed to be much earlier and could involves regions of the peripheral and the central nervous system in addition to the dopaminergic neurons of the SN in the late PD stage. The understanding of this complexity of the pathogenesis is essential for the early diagnosis and for identifying potential targets for more effective medication in early PD phase.

The animal models are indispensable for elucidation of pathomechanisms and essential tools for identifying medical targets for human diseases. The identification of PD-linked genes like the parkin, a-synuclein and other genes provides us a rational basis to model the disease in mice by genetic manipulations. Our previous studies demonstrate that parkin and a-synuclein transgenic mice created in our lab recapture most PD symptoms of the premotor phase, such like anxiety, cognitive impairment, mitochondrial defects and others. Because their accurate and selective modification in a complexity, our mouse models offer an ideal system for the transcriptome analysis in order to approach changes in the gene expression pattern of the entire genome that is selectively related to the premotor pathogenic process of PD.

contact person: Dr. Xinran Zhu