Oligodendrocyte degeneration and concomitant microglia activation directs peripheral immune cells into the forebrain

Uta Chrzanowski, Sudip Bhattarai, Miriam Scheld, Tim Clarner, Petra Fallier-Becker, Cordian Beyer, Sven Olaf Rohr, Christoph Schmitz, Tanja Hochstrasser, Felix Schweiger, Sandra Amor, Anja Horn-Bochtler, Bernd Denecke, Stella Nyamoya, Markus Kipp

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Brain-intrinsic degenerative cascades are a proposed factor driving inflammatory lesion formation in multiple sclerosis (MS) patients. We recently showed that encephalitogenic lymphocytes are recruited to the sites of active demyelination induced by cuprizone. Here, we investigated whether cuprizone-induced oligodendrocyte and myelin pathology is sufficient to trigger peripheral immune cell recruitment into the forebrain. We show that early cuprizone-induced white matter lesions display a striking similarity to early MS lesions, i.e., oligodendrocyte degeneration, microglia activation and absence of severe lymphocyte infiltration. Such early cuprizone lesions are sufficient to trigger peripheral immune cell recruitment secondary to subsequent EAE (experimental autoimmune encephalomyelitis) induction. The lesions are characterized by discontinuation of the perivascular glia limitans, focal axonal damage, and perivascular astrocyte pathology. Time course studies showed that the severity of cuprizone-induced lesions positively correlates with the extent of peripheral immune cell recruitment. Furthermore, results of genome-wide array analyses suggest that moesin is integral for early microglia activation in cuprizone and MS lesions. This study underpins the significance of brain-intrinsic degenerative cascades for immune cell recruitment and, in consequence, MS lesion formation.
Original languageEnglish
Pages (from-to)139-153
Number of pages15
JournalNeurochemistry International
Volume126
DOIs
Publication statusPublished - 1 Jun 2019

Cite this

Chrzanowski, U., Bhattarai, S., Scheld, M., Clarner, T., Fallier-Becker, P., Beyer, C., ... Kipp, M. (2019). Oligodendrocyte degeneration and concomitant microglia activation directs peripheral immune cells into the forebrain. Neurochemistry International, 126, 139-153. https://doi.org/10.1016/j.neuint.2019.03.005