Trafficking of immune cells across the bloodbrain barrier is modulated by neurofibrillary pathology in tauopathies

Petra Majerova, Alena Michalicova, Martin Cente, Jozef Hanes, Jozef Vegh, A. Kittel, Nina Kosikova, Viera Cigankova, Sandra Mihaljevic, Santosh Jadhav, Andrej Kovac

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Tauopathies represent a heterogeneous group of neurodegenerative disorders characterized by abnormal deposition of the hyperphosphorylated microtubule-associated protein tau. Chronic neuroinflammation in tauopathies is driven by glial cells that potentially trigger the disruption of the blood-brain barrier (BBB). Pro-inflammatory signaling molecules such as cytokines, chemokines and adhesion molecules produced by glial cells, neurons and endothelial cells, in general, cooperate to determine the integrity of BBB by influencing vascular permeability, enhancing migration of immune cells and altering transport systems. We considered the effect of tau about vascular permeability of peripheral blood cells in vitro and in vivo using primary rat BBB model and transgenic rat model expressing misfolded truncated protein tau. Immunohistochemistry, electron microscopy and transcriptomic analysis were employed to characterize the structural and functional changes in BBB manifested by neurofibrillary pathology in a transgenic model. Our results show that misfolded protein tau ultimately modifies the endothelial properties of BBB, facilitating blood-to-brain cell transmigration. Our results suggest that the increased diapedesis of peripheral cells across the BBB, in response to tau protein, could be mediated by the increased expression of endothelial signaling molecules, namely ICAM-1, VCAM-1, and selectins. We suggest that the compensation of BBB in the diseased brain represents a crucial factor in neurodegeneration of human tauopathies.

Original languageEnglish
Article numbere0217216
JournalPloS one
Volume14
Issue number5
DOIs
Publication statusPublished - May 1 2019

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'Trafficking of immune cells across the bloodbrain barrier is modulated by neurofibrillary pathology in tauopathies'. Together they form a unique fingerprint.

  • Cite this

    Majerova, P., Michalicova, A., Cente, M., Hanes, J., Vegh, J., Kittel, A., Kosikova, N., Cigankova, V., Mihaljevic, S., Jadhav, S., & Kovac, A. (2019). Trafficking of immune cells across the bloodbrain barrier is modulated by neurofibrillary pathology in tauopathies. PloS one, 14(5), [e0217216]. https://doi.org/10.1371/journal.pone.0217216