Studies on structural and functional changes of mouse choroid plexus in the initiation of neuroinflammation
Значај структурних и функционалних промена хороидног плексуса миша у иницијацији неуроинфламације
Doktorand
Brkić, MarjanaMentor
Vandenbroucke, RoosmarijnČlanovi komisije
Kanazir, SelmaNedeljković, Nadežda
Anđus, Pavle
Libert, Claude
Metapodaci
Prikaz svih podataka o disertacijiSažetak
Neuroinflammation has been considered a common denominator and crucial
player in neurodegeneration observed in various central nervous system (CNS)
disorders. Considering the increasing evidence on the role of choroid plexus (CP) in
neuroinflammatory processes through alterations in morphology and functionality of
the choroid plexus epithelial (CPE) cells, the main goal of this thesis was to test the
contribution of the CP in the initiation of neuroinflammation in two animal models of
neuroinflammation-associated diseases: a model of Alzheimer’s disease, induced by
intracerebroventricularly (i.c.v.) injected amyloid beta oligomers (AβO) and a
lipopolysaccharide (LPS) induced sepsis animal model of systemic inflammation. Main
findings from this research conclude that blood cerebrospinal fluid barrier (BCSFB)
permeability is increased upon AβO injection, resulting from the loss of typical cuboidal
morphology of CPE cells and a decrease in expression of tight junctions components. In
the ...CP, upregulation of gene expression for various cytokines was observed, as well as
their increased levels in the cerebrospinal fluid (CSF). Also, increase in gene expression
for several matrix metalloproteinases (MMP) in the CP, and in MMP activity in the CSF
was noted. After i.c.v. injection of broad spectrum MMP inhibitor with AβO, prevention
of AβO-induced BCSFB permeability was found. In accordance with this, increase in
BCSFB permeability upon AβO injection was observed in MMP3 deficient mice, but to a
lesser extent. Furthermore, an increase in the number of particles in the CSF and an
increase in gene expression of extracellular vesicles (EV) markers and miR-155 was
found in the CP. A similar pattern of changes in the CP was observed in response to LPS
injection compared to AβO injection. The results of this study revealed a significant role
for the CP in the initiation of neuroinflammation, through structural and functional
changes, in two different models associated with neuroinflammation.