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Effect of Anti-infl...
Effect of Anti-inflammatory Treatment with AMD3100 and CX3CR1 Deficiency on GABAA Receptor Subunit and Expression of Glutamate Decarboxylase Isoforms After Stroke
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- Michalettos, Georgios (author)
- Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Laboratory for Experimental Brain Research,Forskargrupper vid Lunds universitet,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Walter, Helene L. (author)
- Lund University,University of Cologne
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- Antunes, Ana Rita Pombo (author)
- Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Wieloch, Tadeusz (author)
- Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Laboratory for Experimental Brain Research,Forskargrupper vid Lunds universitet,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Talhada, Daniela (author)
- Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Laboratory for Experimental Brain Research,Forskargrupper vid Lunds universitet,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Ruscher, Karsten (author)
- Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,Forskargrupper vid Lunds universitet,Laboratory for Experimental Brain Research,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research,Lund University Research Groups
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(creator_code:org_t)
- 2021-08-20
- 2021
- English.
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In: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 58:11, s. 5876-5889
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Abstract
Subject headings
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- Following stroke, attenuation of detrimental inflammatory pathways might be a promising strategy to improve long-term outcome. In particular, cascades driven by pro-inflammatory chemokines interact with neurotransmitter systems such as the GABAergic system. This crosstalk might be of relevance for mechanisms of neuronal plasticity, however, detailed studies are lacking. The purpose of this study was to determine if treatment with 1,1′-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane] (AMD3100), an antagonist to the C-X-C chemokine receptor type 4 (CXCR4) and partial allosteric agonist to CXCR7 (AMD3100) alone or in combination with C-X3-C chemokine receptor type 1 (CX3CR1) deficiency, affect the expression of GABAA subunits and glutamate decarboxylase (GAD) isoforms. Heterozygous, CX3CR1-deficient mice and wild-type littermates were subjected to photothrombosis (PT). Treatment with AMD3100 (0.5 mg/kg twice daily i.p.) was administered starting from day 2 after induction of PT until day 14 after the insult. At this time point, GABAA receptor subunits (α3, β3, δ), GAD65 and GAD67, and CXCR4 were analyzed from the peri-infarct tissue and homotypic brain regions of the contralateral hemisphere by quantitative real-time PCR and Western Blot. Fourteen days after PT, CX3CR1 deficiency resulted in a significant decrease of the three GABAA receptor subunits in both the lesioned and the contralateral hemisphere compared to sham-operated mice. Treatment with AMD3100 promoted the down-regulation of GABAA subunits and GAD67 in the ipsilateral peri-infarct area, while the β3 subunit and the GAD isoforms were up-regulated in homotypic regions of the contralateral cortex. Changes in GABAA receptor subunits and GABA synthesis suggest that the CXCR4/7 and CX3CR1 signaling pathways are involved in the regulation of GABAergic neurotransmission in the post-ischemic brain.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- AMD3100
- CX3CR1
- CXCR4
- GABA
- Glutamate decarboxylase
- Inhibition
- Neuronal plasticity
- Stroke recovery
Publication and Content Type
- art (subject category)
- ref (subject category)
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