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Activation of dopamine 2 receptors modulates glutamate decarboxylases 65 and 67 during stroke recovery in mice

Neuroprotection 2023年第2期1卷 160-169页

作者： Daniela Talhada Robert Nilsson severin walser Georgios Michalettos Karsten Ruscher Laboratory for Experimental Brain Research Department of Clinical SciencesDivision of NeurosurgeryLund UniversityLundSweden LUBIN Lab-Lunds Laboratorium för Neurokirurgisk Hjärnskadeforskning Department of Clinical SciencesDivision of NeurosurgeryLund UniversityLundSweden

Backgrounds:Treatment with levodopa enhances recovery of lost neurological functions in preclinical stroke models and ***,we studied whether dopamine signaling modulates GABAergic neurotransmission in parvalbumin-positive interneurons after experimental ***:Following block randomization,mice were subjected to experimental stroke induced by photothrombosis(PT).Two days after the insult,mice were treated either with the D1 receptor antagonist by R(+)-SCH-23390(0.1 mg/kg),the selective D1 receptor agonist(R)-(+)-SKF-38393 hydrochloride(1 mg/kg),the D2 receptor agonist R(−)-2,10,11-trihydroxy-Npropyl-noraporphine hydrobromide hydrate(TNPA)(1 mg/kg),the D2 receptor antagonist S-(−)-eticlopride hydrochloride(0.3 mg/kg),or vehicle(saline)by daily intraperitoneal injection for five consecutive days,*** of function was assessed by paw placement and foot fault test before and on Days 2 and 7 after ***:Mice treated with TNPA showed a statistically significant improvement of recovery compared to all other treatment *** of gamma-aminobutyric acid(GABA)was quantified by levels of full-length and cleaved glutamate acid decarboxylase 67 and 65(GAD65 and GAD67)in the peri-infarct area and homotypic regions of the contralateral *** to the other treatments,TNPA significantly reduced the level of the GAD67 isoform both in the ischemic and contralateral *** of GAD65 were found significantly higher in the contralateral hemisphere in TNPA-treated mice after PT accompanied by an increase in the 58 kDa-truncated ***:Our results point toward reduced GABA synthesis in a D2 receptor-mediated mechanism possibly contributing to counteract functional inhibition after stroke.

关键词： calpain dopamine glutamate decarboxylase photothrombosis stroke recovery

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