Sonic hedgehog is a regulator of extracellular glutamate levels and epilepsy.

Abstract:

:Sonic hedgehog (Shh), both as a mitogen and as a morphogen, plays an important role in cell proliferation and differentiation during early development. Here, we show that Shh inhibits glutamate transporter activities in neurons, rapidly enhances extracellular glutamate levels, and affects the development of epilepsy. Shh is quickly released in response to epileptic, but not physiological, stimuli. Inhibition of neuronal glutamate transporters by Shh depends on heterotrimeric G protein subunit Gαi and enhances extracellular glutamate levels. Inhibiting Shh signaling greatly reduces epileptiform activities in both cell cultures and hippocampal slices. Moreover, pharmacological or genetic inhibition of Shh signaling markedly suppresses epileptic phenotypes in kindling or pilocarpine models. Our results suggest that Shh contributes to the development of epilepsy and suppression of its signaling prevents the development of the disease. Thus, Shh can act as a modulator of neuronal activity, rapidly regulating glutamate levels and promoting epilepsy.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Feng S,Ma S,Jia C,Su Y,Yang S,Zhou K,Liu Y,Cheng J,Lu D,Fan L,Wang Y

doi

10.15252/embr.201541569

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

682-94

issue

5

eissn

1469-221X

issn

1469-3178

pii

embr.201541569

journal_volume

17

pub_type

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