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Open AccessArticle

Astroglial Connexin 43 Deficiency Protects against LPS-Induced Neuroinflammation: A TSPO Brain µPET Study with [18F]FEPPA

1
Université de Paris, Faculté de Santé, Institut de Recherche Saint-Louis, Unité Claude Kellershohn, 75010 Paris, France
2
INSERM UMR-S 1144, Therapeutic Optimisation in Neuropsychopharmacology, 75005 Paris, France
3
Assistance Publique – Hôpitaux de Paris, Hôpital Lariboisière: Service de médecine nucléaire, 75010 Paris, France
4
Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, PSL Research University, 75005 Paris, France
5
Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Louis: Service Pharmacie, Unité Claude Kellershohn, 75010 Paris, France
6
Université de Paris, Faculté de Santé, 75005 Paris, France
7
Assistance Publique – Hôpitaux de Paris, Hôpital Cochin: Service de biologie du médicament et de toxicologie, 75014 Paris, France
8
Assistance Publique – Hôpitaux de Paris, Hôpital Necker – Enfants Malades: Service de pharmacie, 75015 Paris, France
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 389; https://doi.org/10.3390/cells9020389
Received: 31 December 2019 / Revised: 27 January 2020 / Accepted: 3 February 2020 / Published: 7 February 2020
(This article belongs to the Special Issue Astroglial Connexin Physiology)
Astroglial connexin 43 (Cx43) has been recognized as a crucial immunoregulating factor in the brain. Its inactivation leads to a continuous immune recruitment, cytokine expression modification and a specific humoral autoimmune response against the astrocytic extracellular matrix but without brain lesions or cell lysis. To assess the impact of Cx43 deletion on the brain’s inflammatory response, TSPO expression was studied by positron emission tomography (PET) imaging with a specific radioligand, [18F]FEPPA, in basal conditions or upon Lipopolysaccharides (LPS)-induced inflammatory challenge. Astroglial Cx43-deleted mice underwent [18F]FEPPA PET/CT dynamic imaging with or without LPS injection (5 mg/kg) 24 h before imaging. Quantification and pharmacokinetic data modelling with a 2TCM-1K compartment model were performed. After collecting the mice brains, TSPO expression was quantified and localized by Western blot and FISH analysis. We found that astroglial Cx43 deficiency does not significantly alter TSPO expression in the basal state as observed with [18F]FEPPA PET imaging, FISH and Western blot analysis. However, deletion of astrocyte Cx43 abolishes the LPS-induced TSPO increase. Autoimmune encephalopathy observed in astroglial Cx43-deleted mice does not involve TSPO overexpression. Consistent with previous studies showing a unique inflammatory status in the absence of astrocyte Cx43, we show that a deficient expression of astrocytic Cx43 protects the animals from LPS-induced neuroinflammation as addressed by TSPO expression.
Keywords: [18F]FEPPA; astrocytes; autoimmunity; blood–brain barrier; brain inflammation; Connexin 43; PET imaging; TSPO [18F]FEPPA; astrocytes; autoimmunity; blood–brain barrier; brain inflammation; Connexin 43; PET imaging; TSPO
MDPI and ACS Style

Vignal, N.; Boulay, A.-C.; San, C.; Cohen-Salmon, M.; Rizzo-Padoin, N.; Sarda-Mantel, L.; Declèves, X.; Cisternino, S.; Hosten, B. Astroglial Connexin 43 Deficiency Protects against LPS-Induced Neuroinflammation: A TSPO Brain µPET Study with [18F]FEPPA. Cells 2020, 9, 389.

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