Sonic hedgehog is a regulator of extracellular glutamate levels and epilepsy
| Autor: | Shenglian Yang, Liu Fan, Ju Cheng, Kechun Zhou, Caixia Jia, Yujuan Su, Yani Liu, Shaorong Ma, Yizheng Wang, Shengjie Feng, Dunguo Lu |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine animal structures Gi alpha subunit Regulator Glutamic Acid GTP-Binding Protein alpha Subunits Gi-Go Pharmacology Hippocampus Zinc Finger Protein GLI1 Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Genetics Animals Premovement neuronal activity Hedgehog Proteins Sonic hedgehog Receptor Molecular Biology Cerebral Cortex Mice Knockout Neurons Epilepsy biology Pyramidal Cells Scientific Reports Glutamate receptor Rats Cell biology Disease Models Animal 030104 developmental biology Mitogen-activated protein kinase embryonic structures biology.protein Calcium Extracellular Space 030217 neurology & neurosurgery Signal Transduction Morphogen |
| Zdroj: | EMBO reports. 17:682-694 |
| ISSN: | 1469-3178 1469-221X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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