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0This research article investigates how Survival Motor Neuron (SMN) protein deficiency causes structural and functional impairments in the motor cortex of Spinal Muscular Atrophy (SMA) mouse models. The authors demonstrate that a lack of SMN disrupts the excitatory-inhibitory balance by significantly reducing the density, morphology, and signaling of GABAergic parvalbumin-positive interneurons. This dysfunction is linked to metabolic failures in the neuron-astrocyte glutamate-glutamine cycle, specifically involving the downregulation of the SNAT5 transporter and synthesis enzymes. Electrophysiological data confirm that these alterations lead to impaired activity-dependent inhibitory neurotransmission onto pyramidal neurons, contributing to upper motor neuron vulnerability. Ultimately, the study suggests that restoring SMN levels with Nusinersen can modulate these pathways, highlighting the motor cortex as a critical target for comprehensive SMA therapies.
References:
Menduti G, Ferrini F, Caretto A, et al. Changes in the cortical GABAergic inhibitory system in a Spinal Muscular Atrophy mouse model[J]. Cell Death & Disease, 2026, 17(1): 285.
