Disassembly and Mislocalization of AQP4 in Incipient Scar Formation after Experimental Stroke |
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Authors: | Shervin Banitalebi Nadia Skauli Samuel Geiseler Ole Petter Ottersen Mahmood Amiry-Moghaddam |
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Affiliation: | 1.Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway; (S.B.); (N.S.); (O.P.O.);2.Cardiovascular Research Group IMB, Department of Medical Biology, Faculty of Health Sciences, UiT—The Arctic University of Norway, 9019 Tromsø, Norway;3.President’s Office, Karolinska Institutet, Nobels väg 6, 171 77 Stockholm, Sweden |
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Abstract: | There is an urgent need to better understand the mechanisms involved in scar formation in the brain. It is well known that astrocytes are critically engaged in this process. Here, we analyze incipient scar formation one week after a discrete ischemic insult to the cerebral cortex. We show that the infarct border zone is characterized by pronounced changes in the organization and subcellular localization of the major astrocytic protein AQP4. Specifically, there is a loss of AQP4 from astrocytic endfoot membranes that anchor astrocytes to pericapillary basal laminae and a disassembly of the supramolecular AQP4 complexes that normally abound in these membranes. This disassembly may be mechanistically coupled to a downregulation of the newly discovered AQP4 isoform AQP4ex. AQP4 has adhesive properties and is assumed to facilitate astrocyte mobility by permitting rapid volume changes at the leading edges of migrating astrocytes. Thus, the present findings provide new insight in the molecular basis of incipient scar formation. |
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Keywords: | aquaporin-4 (AQP4) AQP4ex OAP stroke ischemia astrocyte reactive astrogliosis glial scar neuroinflammation |
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