[SCItalk] Synaptic Dysfunction in Spinal Muscular Atrophy Mouse Models
University of Seville, Spain
In spinal muscular atrophy (SMA), a motoneuron disease caused by mutation or loss of the SMN (survival of motor neuron) gene, and leading genetic cause of infant mortality, the motor nerve terminal is profoundly altered. We investigated the mechanisms of the dysfunction and found that the neurotransmitter release impairment correlates with a decrease in the number of release sites and the selective decrease of the synaptic proteins SV2B and Synaptotagmin 2 at the neuromuscular junction of vulnerable muscles. Also, the ability of presynaptic mitochondria to handle activity-induced Ca2+ loads was reduced in SMA motor nerve terminals. Our findings suggest that the alterations in mitochondrial calcium dynamics and synaptic vesicle recycling defects are converging pathways in the pathophysiology of SMA motor terminals.
Lucia Tabares, MD, Ph.D., is a Professor in the Department of Medical Physiology and Biophysics of the University of Seville, Spain. The interest of her laboratory is to better understand the cellular and molecular mechanisms that ensure reliable synaptic transmission. We also investigate by electrophysiological and live imaging techniques at the neuromuscular junction the origin of the neurotransmission defects in mouse models of synaptopathy.
Host: Joan Blasi and Carles Solsona - Cellular and Molecular Neurobiology group