Synaptotagmin 4 Supports Spontaneous Axon Sprouting After Spinal Cord Injury

Overview

Journal J Neurosci

Specialty Neurology

Date 2024 Sep 12

PMID 39266302

Authors

Kyoka Higuchi

Akiko Uyeda

Lili Quan

Shogo Tanabe

Yuki Kato

Yukio Kawahara

Rieko Muramatsu

Affiliations

Soon will be listed here.

Abstract

Injuries to the central nervous system (CNS) can cause severe neurological deficits. Axonal regrowth is a fundamental process for the reconstruction of compensatory neuronal networks after injury; however, it is extremely limited in the adult mammalian CNS. In this study, we conducted a loss-of-function genetic screen in cortical neurons, combined with a Web resource-based phenotypic screen, and identified synaptotagmin 4 (Syt4) as a novel regulator of axon elongation. Silencing Syt4 in primary cultured cortical neurons inhibits neurite elongation, with changes in gene expression involved in signaling pathways related to neuronal development. In a spinal cord injury model, inhibition of Syt4 expression in cortical neurons prevented axonal sprouting of the corticospinal tract, as well as neurological recovery after injury. These results provide a novel therapeutic approach to CNS injury by modulating Syt4 function.

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