Professor Giovanna Mallucci, Department of Clinical Neurosciences, University of Cambridge
Tuesday 13th December, 1.00 p.m., Stacey Lecture Theatre 1
Compromised synaptic function underlies the earliest symptoms in several neurodegenerative diseases. It is an early stage in pathogenesis that can be rescued, and is therefore a key therapeutic target for translation. In the healthy adult brain synapses are continually lost and replaced, through plasticity, a process critical for repair that also underlies learning and memory. Plasticity can be elicited by various stimuli. One physiological form of structural plasticity occurs in hibernating squirrels and hamsters. When they enter torpor, hibernators dismantle their synapses, without loss of synaptic proteins. These changes are rapidly reversed when euthermia is achieved, with correct structural and functional reassembly of synapses. To test the capacity for synapse regeneration in neurodegenerative disease, we used the paradigm of cooling-induced structural plasticity that occurs in hibernation. Using mouse models of neurodegeneration, we discovered that 1) that the capacity for cold-induced synaptic repair is impaired in neurodegenerative disease, 2) the role of the ‘cold shock’ protein RBM3 in mediating structural plasticity and 3) the therapeutic potential for manipulation of RBM3 levels for neuroprotection in neurodegenerative diseases.