John Pagiazitis
Catecholaminergic dysfunction drives postural and locomotor deficits in spinal muscular atrophy
Carl Ludwig Institute of Physiology and the Research Group Simon cordially invite you to the talk:
- John Pagiazitis
Center for Motor Neuron Biology and Disease & Department of Neurology, Columbia University, New York, NY, USA
"Catecholaminergic dysfunction drives postural and locomotor deficits in a mouse model of spinal muscular atrophy"
07th February 2025, 09:00
Carl Ludwig Institute of Physiology, Seminar Room E215, 2nd floor, Liebigstraße 27a, 04103 Leipzig
Abstract:
Development and maintenance of posture is essential behavior for overground mammalian locomotion. Dopamine and noradrenaline strongly influence locomotion, and their dysregulation initiates the develop-ment of motor impairments linked to neurodegenerative disease. However, the precise cellular and circuit mechanisms are not well defined. Here, we investigated the role of catecholaminergic neuromodulation in a mouse model of spinal muscular atrophy (SMA). SMA is characterized by severe motor dysfunction and postural deficits. We identify progressive loss of catecholaminergic synapses from spinal neurons that occur via non-cell autonomous mechanisms. Importantly, the selective restoration of survival motor neuron (SMN) in either catecholaminergic or serotonergic neurons is sufficient to correct impairments in locomotion. How-ever, only combined SMN restoration in both catecholaminergic and serotonergic neurons or pharmacolog-ical treatment with L-dopa improve the severe postural deficits. These findings uncover the synaptic and cellular mechanisms responsible for the postural and motor symptoms in SMA and identify catecholaminergic neuromodulation as a potential therapeutic target.