Universität zu Köln

Michalettos, Georgios, Walter, Helene L., Antunes, Ana Rita Pombo, Wieloch, Tadeusz, Talhada, Daniela and Ruscher, Karsten (2021). Effect of Anti-inflammatory Treatment with AMD3100 and CX(3)CR1 Deficiency on GABA(A) Receptor Subunit and Expression of Glutamate Decarboxylase Isoforms After Stroke. Mol. Neurobiol., 58 (11). S. 5876 - 5890. NEW YORK: SPRINGER. ISSN 1559-1182

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Abstract

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 GABA(A) 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, GABA(A) receptor subunits (alpha 3, beta 3, delta), 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 GABA(A) receptor subunits in both the lesioned and the contralateral hemisphere compared to sham-operated mice. Treatment with AMD3100 promoted the down-regulation of GABA(A) subunits and GAD67 in the ipsilateral peri-infarct area, while the beta 3 subunit and the GAD isoforms were up-regulated in homotypic regions of the contralateral cortex. Changes in GABA(A) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Michalettos, Georgios UNSPECIFIED UNSPECIFIED UNSPECIFIED Walter, Helene L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Antunes, Ana Rita Pombo UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieloch, Tadeusz UNSPECIFIED UNSPECIFIED UNSPECIFIED Talhada, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruscher, Karsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-572161
DOI:	10.1007/s12035-021-02510-x
Journal or Publication Title:	Mol. Neurobiol.
Volume:	58
Number:	11
Page Range:	S. 5876 - 5890
Date:	2021
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1559-1182
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOCAL CEREBRAL-ISCHEMIA; FRACTALKINE-RECEPTOR; FUNCTIONAL RECOVERY; ACID DECARBOXYLASE; INHIBITION; PLASTICITY; BRAIN; INFLAMMATION; MECHANISMS; SUBTYPES Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57216