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

作　　者：Daniela Talhada Robert Nilsson Severin Walser Georgios Michalettos Karsten Ruscher 

机构地区：[1]Laboratory for Experimental Brain Research,Department of Clinical Sciences,Division of Neurosurgery,Lund University,Lund,Sweden [2]LUBIN Lab-Lunds Laboratorium för Neurokirurgisk Hjärnskadeforskning,Department of Clinical Sciences,Division of Neurosurgery,Lund University,Lund,Sweden

出　　处：《Neuroprotection》2023年第2期160-169,共10页神经保护（英文）

基　　金：Swedish Brain Fund,Grant/Award Numbers:FO2020-0138,FO2022-0154;Hans-Gabriel and Alice Trolle Wachtmeister Foundation;Skåne(ALF);Crafoord Foundation。

摘　　要：Backgrounds:Treatment with levodopa enhances recovery of lost neurological functions in preclinical stroke models and patients.Here,we studied whether dopamine signaling modulates GABAergic neurotransmission in parvalbumin-positive interneurons after experimental stroke.Methods: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,respectively.Recovery of function was assessed by paw placement and foot fault test before and on Days 2 and 7 after surgery.Results:Mice treated with TNPA showed a statistically significant improvement of recovery compared to all other treatment conditions.Synthesis 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 cortex.Compared to the other treatments,TNPA significantly reduced the level of the GAD67 isoform both in the ischemic and contralateral hemispheres.Levels 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 form.Conclusion: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 

分 类 号：R743.3[医药卫生—神经病学与精神病学]