ZOË BICHLER, Ph.D.Associate Research Scientist, Behavioural Neuroscience LaboratoryAdjunct Assistant Professor at Duke-NUS Medical School
Behavioural Neuroscience LaboratoryNational Neuroscience Institute11 Jalan Tan Tock Seng, Singapore 308433 Tel: (65) 6357 7128 (Office) Fax:(65) 6256 9178
Our laboratory’s interests lie in understanding the etiopathogenesis of psychiatric and neurodegenerative diseases, by investigating the behavioural and neurobiochemical changes of transgenic mouse models in relation with genetic and environmental factors. Phenotypic analysis are conducted by means of a large battery of behavioural and biochemical assays. They include measurements of motor abilities, sensorial functions (tactile, vision, olfaction), pain sensitivity, gastrointestinal functions, mood disorders, social interactions and cognitive abilities, as well as specific protein analysis in brain samples, especially by immunohistochemistry assays followed by stereological analysis.
Our main project tries to understand the causes and development of Parkinson’s disease. This neurodegenerative disease is diagnosed according to motor features, that appear relatively late in the time course of the disease. At this stage, irreversible neurochemical changes in the brain are well advanced: dopaminergic cells are degenerating in the substantia nigra, Lewy bodies appear and the neurotransmission in the brain is deregulated. Treatments improve the symptoms but cannot slow down or halt the progression of the disease course. Patients suffer also from several non-motor disorders, which often precede the motor symptoms. Identifying early non-motor-behavioural markers would improve significantly the treatment of patients. To find possible correlations between motor and non-motor dysfunctions, we conduct longitudinal studies of several mouse lines carrying specific pathogenic mutations of the human LRRK2 gene, known to be a risk factor for Parkinson’s disease. In addition to the common LRRK2 variants (i.e. G2019S, R1441G), we investigate the contribution of LRRK2 genetic mutations specific to the Chinese population (R1628P and G2385R, Tan E.K., et al., 2010: Human Mutation, Vol. 31, No. 5, 561–568). Since the penetrance and expression of the genes involved in Parkinson’s disease are likely to be modified by environmental factors, we apply a series of additional stresses, which, combined to the expression of a pathogenic mutation, might enhance the severity of the pathology in our mouse models.
This research is conducted in close collaboration with Professor Tan Eng King, Research Director, NNI and Senior Consultant, Department of Neurology, NNI (SGH Campus). By comparing our data with clinical studies, we hope to be able to find specific symptoms that might serve as early clinical markers helping to diagnose Parkinson’s disease earlier in patients.
Significance of Our Research to Patients
Parkinson’s disease is the most common neurodegenerative disease seen at the outpatients’ clinics of the National Neuroscience Institute. It concerns more than four million of people worldwide, and its prevalence continues to rise as the population ages. Some LRRK2 genetic mutations such as the R1628P and G2385R pathogenic variants account for between 5 to 40% of the entire Chinese population, i.e. about 400 million carriers worldwide. Hence, better understandings of the correlation between non-motor and motor disorders and the pathophysiology of these variants have immense potential in early diagnosis, monitoring and treatment. The results of our research should bring long term benefits and better health outcomes in our society, in particular in Singapore.
Other projects of the laboratory include:
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