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 Repjournal_title
EMBO reportsauthors
Feng S,Ma S,Jia C,Su Y,Yang S,Zhou K,Liu Y,Cheng J,Lu D,Fan L,Wang Ydoi
10.15252/embr.201541569subject
Has Abstractpub_date
2016-05-01 00:00:00pages
682-94issue
5eissn
1469-221Xissn
1469-3178pii
embr.201541569journal_volume
17pub_type
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