Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Disassembly and Mislocalization of AQP4 in Incipient Scar Formation After Experimental Stroke

Version 1 : Received: 2 January 2022 / Approved: 6 January 2022 / Online: 6 January 2022 (10:16:02 CET)

A peer-reviewed article of this Preprint also exists.

Banitalebi, S.; Skauli, N.; Geiseler, S.; Ottersen, O.P.; Amiry-Moghaddam, M. Disassembly and Mislocalization of AQP4 in Incipient Scar Formation after Experimental Stroke. Int. J. Mol. Sci. 2022, 23, 1117. Banitalebi, S.; Skauli, N.; Geiseler, S.; Ottersen, O.P.; Amiry-Moghaddam, M. Disassembly and Mislocalization of AQP4 in Incipient Scar Formation after Experimental Stroke. Int. J. Mol. Sci. 2022, 23, 1117.

Abstract

There is an urgent need to better understand the mechanisms involved in scar formation in brain. It is well known that astrocytes are critically engaged in this process. Here we analyze in-cipient 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 mo-bility 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.

Keywords

Aquaporin-4; AQP4ex; Stroke; Ischemia; Astrocyte; Astrogliosis; Glial scar; Neuroinflammation

Subject

Medicine and Pharmacology, Neuroscience and Neurology

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