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The serotonin transporter is a regulator of neurodegeneration and axon regeneration after retinal injury

ABSTRACT: Loss of specialized neurons in neurodegenerative diseases and after nerve injury is mediated in a neuronal subtype- and region-specific fashion. However, little is known about what molecular contexts define selective vulnerability. Here, we demonstrate that retinal ganglion cells (RGCs) in the mouse peripheral ventrotemporal (VT) retina are the most susceptible to optic nerve injury. Mechanistically, we show that the ventral-specific molecule, the serotonin transporter (SERT) is upregulated on VT axons within one day after injury and loss of SERT attenuates VT RGC death and promotes axon regeneration. From RNA-seq analysis, the transmembrane protein Gpnmb has been identified as a target downregulated by SERT. Moreover, GPNMB is involved in RGC protection and axon regeneration. Together, our studies reveal the serotonin transporter as a determinant of selective vulnerability.

ORGANISM(S): Mus musculus

PROVIDER: GSE153812 | GEO | 2020/07/11

REPOSITORIES: GEO

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