Importance of the blood-cerebrospinal fluid barrier in Alzheimer’s disease.
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1
VIB, Inflammation Research Center, Belgium
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2
Ghent University, Department of Biomedical Molecular Biology, Belgium
The blood-cerebrospinal fluid (CSF) barrier forms a unique interface between blood and brain. It consists of a single cell layer, called choroid plexus epithelium (CPE), situated at the interface of blood and CSF. The CPE forms a barrier to protect the brain from fluctuations in peripheral blood thereby assuring brain homeostasis, produces CSF and is responsible for the active removal of toxic molecules from the brain. In recent years, the blood-CSF barrier has gained increasing attention, especially its role in inflammatory and age-related diseases.
We studied barrier integrity of the CPE during Alzheimer’s disease. Aβ1-42 oligomers, a key player in the pathology of AD, were injected intracerebroventricular in mice to assess their impact on the blood-CSF barrier. The study revealed the induction of a cascade of detrimental events, associated with loss of blood-CSF barrier integrity. Administration of Aβ1-42 oligomers triggered an inflammatory response at the CPE cells and secretion of proinflammatory cytokines into the CSF. Furthermore, Aβ1-42 oligomers rapidly affected CPE cell morphology and induced a decrease in RNA and protein expression of tight junctions. Finally, using a broad-spectrum matrix metalloproteinase (MMP) inhibitor, we provide evidence for the essential role of MMPs in the Aβ1-42 oligomer-induced loss of blood-CSF barrier integrity.
In conclusion, our results provide new insights in the toxicity of Aβ1-42 oligomers and point to new possible molecular targets to reduce neuroinflammation associated with Alzheimer’s disease.
Résumé en Français :
Dans ce travail nous étudions la modification de l’intégrité de la barrière hémato-encéphalique provoquée lors de la maladie d’Alzheimer. Pour approcher de manière expérimentale, nous avons utilisé des souris et montré que l’injection de l’oligomère Aβ1-42, une molécule clé de la maladie d’Alzheimer, dans les ventricules du cerveau de souris induisait une réponse inflammatoire des cellules de la barrière, une modification de leur morphologie, un affaiblissement de leur jonctions serrées et l’activation de protéases qui diminuent l’intégrité de la barrière.
Samenvatting in het Nederlands:
Dit werk bestudeert de wijziging van de integriteit van de hemato-encefalische afscherming bij de Ziekte van Alzheimer. Ten experimentele titel hebben we gebruik gemaakt van muizen bij wie we het oligomeer Aβ1-42, een sleutelmolecule bij de ziekte van Alzheimer, geïnjecteerd hebben in de hersenholtes van de muizen. Het leidde tot een inflammatoire reactie van de cellen, een wijziging van hun vorm, een verzwakking van hun nauwe verbindingen en een activering van de proteasen die de integriteit van de afscherming verminderen.
Keywords:
Alzheimer's disease,
Blood-Brain Barrier,
Choroid Plexus,
Matrix Metalloproteinases,
Tight Junctions
Conference:
6th Belgian Brain Congress, MONS, Belgium, 8 Oct - 8 Oct, 2016.
Presentation Type:
Poster Presentation
Topic:
Brain and brain diseases: between heredity and environment
Citation:
Brkic
M,
Balusu
S,
Libert
C and
Vandenbroucke
RE
(2016). Importance of the blood-cerebrospinal fluid barrier in Alzheimer’s disease..
Conference Abstract:
6th Belgian Brain Congress.
doi: 10.3389/conf.fnagi.2016.03.00088
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Received:
21 Aug 2016;
Published Online:
22 Aug 2016.
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Correspondence:
Prof. Roosmarijn E Vandenbroucke, VIB, Inflammation Research Center, Zwijnaarde, 9052, Belgium, Roosmarijn.Vandenbroucke@irc.VIB-UGent.be