Connexin43 and connexin47 alterations after neural precursor cells transplantation in experimental autoimmune encephalomyelitis.
Exogenous transplanted neural precursor cells (NPCs) exhibit miscellaneous immune-modulatory effects in models of autoimmune demyelination. However, the regional interactions of NPCs with the host brain tissue in remissive inflammatory events have not been adequately studied. In this study we used the chronic MOG-induced Experimental Autoimmune Encephalomyelitis (EAE) model in C57BL/six mice. Based on previous data, we focused on neuropathology at Day 50 post-induction (D50) and studied the expression of connexin43 (Cx43) and Cx47, two of the main glial gap junction (GJ) proteins, in relation to the intraventricular transplantation of GFP(+) NPCs and their integration with the host tissue. By D50, NPCs had migrated intraparenchymally and were found in the corpus callosum at the level of the lateral ventricles and hippocampus. The majority of GFP(+) cells differentiated with simple or ramified processes expressing mainly markers of mature GLIA (GFAP and NogoA) and significantly less of precursor glial cells. GFP(+) NPCs expressed connexins and formed GJs around the hippocampus more than lateral ventricles. The presence of NPCs did not alter the increase in Cx43 GJ plaques at D50 EAE, but prevented the reduction of oligodendrocytic Cx47, increased the number of oligodendrocytes, local Cx47 levels and Cx47 GJ plaques per cell. These findings suggest that transplanted NPCs may have multiple effects in demyelinating pathology, including differentiation and direct integration into the panglial syncytium, as well as amelioration of oligodendrocyte GJ loss, increasing the supply of potent myelinating cells to the demyelinated tissue.
B' Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Paschalis
P
Theotokis
Neurology Clinics and Neuroscience Laboratory, the Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Kleopas A
KA
Kleopa
B' Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Olga
O
Touloumi
B' Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Roza
R
Lagoudaki
B' Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Athanasios
A
Lourbopoulos
B' Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Evangelia
E
Nousiopoulou
B' Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Evangelia
E
Kesidou
B' Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Kyriaki-Nepheli
KN
Poulatsidou
Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
Efthimios
E
Dardiotis
Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
Georgios
G
Hadjigeorgiou
B' Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Dimitris
D
Karacostas
UMR-S 839 INSERM/UPMC, and the Institut Du Fer À Moulin, Paris, France.
Carmen
C
Cifuentes-Diaz
UMR-S 839 INSERM/UPMC, and the Institut Du Fer À Moulin, Paris, France.
Theano
T
Irinopoulou
B' Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Nikolaos
N
Grigoriadis
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000166:cytology / Q000473:pathology*; D002454:Cell Differentiation; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology / Q000601:surgery*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D004676:Myelin Basic Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology / Q000637:transplantation* / Q000648:ultrastructure; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010446:Peptide Fragments / Q000633:toxicity
D018031:Connexin 43; D017630:Connexins; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C427305:connexin 47; C445081:myelin oligodendrocyte glycoprotein (35-55)
brain; experimental autoimmune encephalomyelitis; gap junctions; glial cells; neural precursor cells