Details

Autor(en) / Beteiligte

• Gerace, Elisabetta
• Scartabelli, Tania
• Pellegrini-Giampietro, Domenico E.
• Landucci, Elisa

Titel

Tolerance Induced by (S)-3,5-Dihydroxyphenylglycine Postconditioning is Mediated by the PI3K/Akt/GSK3β Signalling Pathway in an In Vitro Model of Cerebral Ischemia

Ist Teil von

• Neuroscience, 2020-05, Vol.433, p.221-229

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] •DHPG postconditioning (PostC) induces tolerance by reducing ROS formation.•DHPG PostC induces neuroprotection through PI3K/Akt/GSK3β activation.•The GSK3β inhibitors are neuroprotective in OGD.•The GSK3β inhibitors can be used as PostC agents. Ischemic postconditioning (PostC) is an endogenous neuroprotective strategy for cerebral ischemia induced by low activation of glutamate receptors. We have previously shown that the application of the mGluR1/5 agonist (S)-3,5-dihydroxyphenylglycine (DHPG) 5 min after 30 min of oxygen and glucose deprivation (OGD) reduces CA1 damage in organotypic hippocampal slices by activating the PI3K–Akt signalling pathway. In order to extend these data, we analysed the production of reactive oxygen species (ROS) and the glycogen synthase kinase 3β (GSK3β) signalling pathway. Our results show that DHPG PostC was associated with a reduction in the formation of ROS that is massively increased 24 h after OGD exposure. This reduction was prevented by the PI3K inhibitor LY294002, indicating that there is a link between the PI3K/Akt pathway and the formation of ROS in the protective mechanisms of PostC. DHPG PostC also induces a transient increased in GSK3β phosphorylation and inactivation that is followed by nuclear accumulation of β-catenin, that probably lead to the up-regulation of neuroprotective genes. Our results propose GSK3β as new target for neuroprotection, therefore, we verified that the two GSK3β inhibitors N-(3-Chloro-4-methylphenyl)-5-(4-nitrophenyl)-1,3,4-oxadiazol-2-amine (TC-G 24) and LiCl are neuroprotective agents in OGD and also can be used as PostC agents.