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Neurodegeneration Triggers Peripheral Immune Cell Recruitment into the Forebrain.

Authors :
Scheld M
Rüther BJ
Große-Veldmann R
Ohl K
Tenbrock K
Dreymüller D
Fallier-Becker P
Zendedel A
Beyer C
Clarner T
Kipp M
Source :
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2016 Jan 27; Vol. 36 (4), pp. 1410-5.
Publication Year :
2016

Abstract

Brain-intrinsic degenerative cascades have been proposed to be an initial factor driving lesion formation in multiple sclerosis (MS). Here, we identify neurodegeneration as a potent trigger for peripheral immune cell recruitment into the mouse forebrain. Female C57BL/6 mice were fed cuprizone for 3 weeks, followed by a period of 2 weeks on normal chow to induce the formation of lesion foci in the forebrain. Subsequent immunization with myelin oligodendrocyte glycoprotein 35-55 peptide, which induces myelin autoreactive T cells in the periphery, resulted in massive immune cell recruitment into the affected forebrain. Additional adoptive transfer experiments together with flow cytometry analysis underline the importance of brain-derived signals for immune cell recruitment. This study clearly illustrates the significance of brain-intrinsic degenerative cascades for immune cell recruitment and MS lesion formation. Additional studies have to address the signaling cascades and mechanistic processes that form the top-down communication between the affected brain area, neurovascular unit, and peripheral immune cells.<br />Significance Statement: We identify neurodegeneration as a potent trigger for peripheral immune cell recruitment into the forebrain. Thus, immune cell recruitment might be a second step during the formation of new inflammatory lesions in multiple sclerosis. A better understanding of factors regulating neurodegeneration-induced immune cell recruitment will pave the way for the development of novel therapeutic treatment strategies.<br /> (Copyright © 2016 the authors 0270-6474/16/361410-06$15.00/0.)

Details

Language :
English
ISSN :
1529-2401
Volume :
36
Issue :
4
Database :
MEDLINE
Journal :
The Journal of neuroscience : the official journal of the Society for Neuroscience
Publication Type :
Academic Journal
Accession number :
26818526
Full Text :
https://doi.org/10.1523/JNEUROSCI.2456-15.2016