Investigation of Neurodevelopmental Deficits of 22 q11.2 Deletion Syndrome with a Patient-iPSC-Derived Blood-Brain Barrier Model.
Cells
; 10(10)2021 09 28.
Article
em En
| MEDLINE
| ID: mdl-34685556
ABSTRACT
The blood-brain barrier (BBB) is important in the normal functioning of the central nervous system. An altered BBB has been described in various neuropsychiatric disorders, including schizophrenia. However, the cellular and molecular mechanisms of such alterations remain unclear. Here, we investigate if BBB integrity is compromised in 22q11.2 deletion syndrome (also called DiGeorge syndrome), which is one of the validated genetic risk factors for schizophrenia. We utilized a set of human brain microvascular endothelial cells (HBMECs) derived from the induced pluripotent stem cell (iPSC) lines of patients with 22q11.2-deletion-syndrome-associated schizophrenia. We found that the solute permeability of the BBB formed from patient HBMECs increases by ~1.3-1.4-fold, while the trans-endothelial electrical resistance decreases to ~62% of the control values. Correspondingly, tight junction proteins and the endothelial glycocalyx that determine the integrity of the BBB are significantly disrupted. A transcriptome study also suggests that the transcriptional network related to the cell-cell junctions in the compromised BBB is substantially altered. An enrichment analysis further suggests that the genes within the altered gene expression network also contribute to neurodevelopmental disorders. Our findings suggest that neurovascular coupling can be targeted in developing novel therapeutical strategies for the treatment of 22q11.2 deletion syndrome.
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Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 22
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Barreira Hematoencefálica
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Células-Tronco Pluripotentes Induzidas
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Transtornos do Neurodesenvolvimento
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article