|
Members |
|
Christine Vande Velde, Ph.D.
CONTACT
CHUM Research Centre
SUMMARY OF RESEARCH ACTIVITIES Amyotrophic lateral sclerosis (ALS) is characterized by the selective loss of motor neurons. Motor neurons are unique in both their metabolic demand and architecture, and both are intricately linked. Efficient transport of cellular cargoes along the axonal process (which can be as much as one meter in length) depends on energy supplied by mitochondria. Furthermore, mitochondria are themselves cargos of axonal transport that must be delivered to the synapse so as to provide the necessary fuel for neurotransmission. Disease pathology includes disturbances in both of these elements, namely disrupted mitochondrial ultrastructure and axonal aggregates in both familial and sporadic ALS cases. Mouse models confirm a defect in the axonal transport of at least one defined cargo, although it remains unknown if broader errors in intracellular trafficking exist. In addition, while various defects in mitochondrial metabolism have been reported, it remains unclear if these defects are unique to motor neurons and how they might participate in disease initiation. To examine how mitochondrial trafficking and axonal transport contribute to disease in vivo, we have generated a new transgenic mouse model in which mitochondria of motor neurons are fluorescently-labeled. These mice, in combination with rodents which develop an ALS-like phenotype, will be examined. Specifically, mitochondrial trafficking, dynamics, and axonal transport will be followed in relation to disease stage using confocal imaging of live motor axons. In addition, since mitochondria from motor neurons are labeled in these animals, motor neuron mitochondria will be isolated and assessed for multiple metabolic parameters. Complementary experiments in motor neuron cultures are also used. STUDIED DISEASES Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a relatively common neurodegenerative disease characterized by the selective loss of motor neurons resulting in progressive muscle weakness and inevitable paralysis, and is fatal within one to five years of onset. SELECTED PUBLICATIONS
R. Rakhit, J. Robertson, C. Vande Velde, P. Horne, D.M. Ruth, J. Griffin, D.W. Cleveland, N.R. Cashman, and A. Chakrabartty. (2007) An immunological epitope selective for pathologically misfolded SOD1 in ALS. Nature Medicine, 13:754-759.
LIENS UTILES Site de la Société SLA du Canada
|
||
Christine Vande Velde is Associate Researcher in the Department of Medicine at the Université de Montréal. She directs the SLA and Motor Neuron Diseases Laboratory located at the CHUM Research Centre.