Faculty Opinions recommendation of Neuritin Mediates Activity-Dependent Axonal Branch Formation in Part via FGF Signaling.
Year: 2018
Type: peer-review
Abstract: Aberrant branch formation of granule cell axons (mossy fiber sprouting) is observed in the dentate gyrus of many patients with temporal lobe epilepsy and in animal models of epilepsy.However, the mechanisms underlying mossy fiber sprouting remain elusive.Based on the hypothesis that seizure-mediated gene expression induces abnormal mossy fiber growth, we screened activity-regulated genes in the hippocampus and found that neuritin, an extracellular protein anchored to the cell surface, was rapidly upregulated after electroconvulsive seizures.Overexpression of neuritin in the cultured rat granule cells promoted their axonal branching.Also, kainic acid-dependent axonal branching was abolished in the cultured granule cells from neuritin knock-out mice, suggesting that neuritin may be involved in activity-dependent axonal branching.Moreover, neuritin knock-out mice showed less-severe seizures in chemical kindling probably by reduced mossy fiber sprouting and/or increased seizure resistance.We found that inhibition of the fibroblast growth factor (FGF) receptor attenuated the neuritin-dependent axonal branching.FGF administration also increased branching in granule neurons, whereas neuritin knock-out mice did not show FGF-dependent axonal branching.In addition, FGF and neuritin treatment enhanced the recruitment of FGF receptors to the cell surface.These findings suggest that neuritin and FGF cooperate in inducing mossy fiber sprouting through FGF signaling.Together, these results suggest that FGF and neuritin-mediated axonal branch induction are involved in the aggravation of epilepsy.
Authors: Stephanie Gupton, Shalini Menon
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4245458192