Astrocytes mediate cell non-autonomous correction of aberrant firing in human FXS neurons.
|Title||Astrocytes mediate cell non-autonomous correction of aberrant firing in human FXS neurons.|
|Publication Type||Journal Article|
|Year of Publication||2023|
|Authors||Sharma SDas, Reddy BKumar, Pal R, Ritakari TE, Cooper JD, Selvaraj BT, Kind PC, Chandran S, Wyllie DJA, Chattarji S|
|Date Published||2023 Apr 04|
Pre-clinical studies of fragile X syndrome (FXS) have focused on neurons, with the role of glia remaining largely underexplored. We examined the astrocytic regulation of aberrant firing of FXS neurons derived from human pluripotent stem cells. Human FXS cortical neurons, co-cultured with human FXS astrocytes, fired frequent short-duration spontaneous bursts of action potentials compared with less frequent, longer-duration bursts of control neurons co-cultured with control astrocytes. Intriguingly, bursts fired by FXS neurons co-cultured with control astrocytes are indistinguishable from control neurons. Conversely, control neurons exhibit aberrant firing in the presence of FXS astrocytes. Thus, the astrocyte genotype determines the neuronal firing phenotype. Strikingly, astrocytic-conditioned medium, and not the physical presence of astrocytes, is capable of determining the firing phenotype. The mechanistic basis of this effect indicates that the astroglial-derived protein, S100β, restores normal firing by reversing the suppression of a persistent sodium current in FXS neurons.
|Alternate Journal||Cell Rep|