Defects in Motoneuron-Astrocyte Interactions in Spinal Muscular Atrophy

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Chunyi ZhouChien-Ping Ko

Abstract

Spinal muscular atrophy (SMA) is a motoneuron disease caused by loss or mutation in Survival of Motor Neuron 1 (SMN1) gene. Recent studies have shown that selective restoration of SMN protein in astrocytes partially alleviates pathology in an SMA mouse model, suggesting important roles for astrocytes in SMA. Addressing these underlying mechanisms may provide new therapeutic avenues to fight SMA. Using primary cultures of pure motoneurons or astrocytes from SMNΔ7 (SMA) and wild-type (WT) mice, as well as their mixed and matched cocultures, we characterized the contributions of motoneurons, astrocytes, and their interactions to synapse loss in SMA. In pure motoneuron cultures, SMA motoneurons exhibited normal survival but intrinsic defects in synapse formation and synaptic transmission. In pure astrocyte cultures, SMA astrocytes exhibited defects in calcium homeostasis. In motoneuron-astrocyte contact cocultures, synapse formation and synaptic transmission were significantly reduced when either motoneurons, astrocytes or both were from SMA mice compared with those in WT motoneurons cocultured with WT astrocytes. The reduced synaptic activity is unlikely due to changes in motoneuron excitability. This disruption in synapse formati...Continue Reading

Citations

Feb 10, 2018·Nature Reviews. Neurology·Ewout J N GroenThomas H Gillingwater
Sep 21, 2017·Frontiers in Cellular Neuroscience·Saravanan ArumugamLucía Tabares
Jul 12, 2017·Annals of Clinical and Translational Neurology·Marc-Olivier Deguise, Rashmi Kothary
Mar 8, 2019·Scientific Reports·Kazuki OhuchiHideaki Hara
Apr 16, 2020·Neurobiology of Disease·Elena AbatiStefania Corti
May 7, 2021·Current Opinion in Neurobiology·Christabel X Tan, Cagla Eroglu
Jun 3, 2021·International Journal of Molecular Sciences·Marc-Olivier DeguiseRashmi Kothary

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