Yes / Sonic Hedgehog (SHH) is a glycoprotein associated with development that is also expressed in the adult CNS and released after brain injury. Since the SHH receptors PTCH1 (patched homolog-1) and SMO (Smoothened) are highly expressed on astrocytes, we hypothesised that SHH regulates astrocyte function. Primary mouse cortical astrocytes derived from embryonic (E15) Swiss mouse cortices, were treated with two chemically distinct agonists of the SHH pathway, which caused astrocytes to elongate and proliferate. These changes are accompanied by decreases in the major astrocyte glutamate transporter, GLT-1 and the astrocyte intermediate filament protein GFAP. Multi-site electrophysiological recordings revealed that the SHH agonist, SAG supressed neuronal firing in astrocyte-neuron co-cultures and this was abolished by the astrocyte metabolic inhibitor ethylfluoroacetate, revealing that SHH stimulation of metabolically-active astrocytes influences neuronal firing. Using 3D co-culture, MAP2 western blotting and immunohistochemistry, we show that SHH-stimulated astrocytes protect neurons from kainate induced cell death. Altogether the results show that SHH regulation of astrocyte function represents an endogenous neuroprotective mechanism. / BBSRC
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/12042 |
| Date | 09 May 2017 |
| Creators | Ugbode, Christopher I., Smith, I., Whalley, B.J., Hirst, W.D., Rattray, Marcus |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Published version |
| Rights | © 2017 The Authors. This is an Open Access article under the terms of the Creative Commons CC-BY License (https://creativecommons.org/licenses/by/4.0/) |
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