Fig. 8: Neuronal GABA signalling and metabolic dysregulation in SM CRTX of SMA mice.
From: Changes in the cortical GABAergic inhibitory system in a Spinal Muscular Atrophy mouse model
Schematic cartoon representing dysregulation of GABA signalling and of metabolic pathway components at the neuronal level in the SM cortex of SMA mice (right) compared to WT controls (left). In brief, from top: In SMA, GABA precursor levels (GLN) are not supplied from astrocytes to SMA cortical neurons due to a significant decrease in SNAT5 transport, whose expression is proportionally correlated to the SMN deficiency. Moreover, GAD synthetic enzyme levels are significantly reduced, and the following lower GABA synthesis leads to dysregulation in GABA vesicular packaging and release (mediated by VGAT) and astrocytic GABA transport (mediated by GAT3, leading to astrocytic GABA accumulation). Downstream, SMA neurons show a lower number of GABAergic inhibitory synapses and a lower IPSC frequency, together with a reduction and morphological alteration of PV+ INs (Image created with BioRender.com).
