A novel in vitro model to study pericytes in the neurovascular unit of the developing cortex

Cortical function is impaired in various disorders of the central nervous system including Alzheimer's disease, autism and schizophrenia. Some of these disorders are speculated to be associated with insults in early brain development. Pericytes have been shown to regulate neurovascular integrit...

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Bibliographic Details
Published in:PloS one 2013-11, Vol.8 (11), p.e81637-e81637
Main Authors: Zehendner, Christoph M, Wedler, Hannah E, Luhmann, Heiko J
Format: Article
Language:English
Subjects:
Animal cognition
Animals
Apoptosis
Autism
Blood-brain barrier
Brain
Brain injury
Caspase
Caspase 3 - metabolism
Caspase-3
Cell fate
Cell Hypoxia
Cell Proliferation
Cell Survival
Central nervous system
Cerebral Cortex - blood supply
Cerebral Cortex - enzymology
Cerebral Cortex - growth & development
Cognitive ability
Cortex
Disease control
Disorders
Evolution
Hypoxia
Inflammation
Inflammation - enzymology
Ischemia
Laboratory animals
Mental disorders
Mice
Mice, Inbred C57BL
Morphology
Mutants
Neuroimaging
Pericytes
Pericytes - cytology
Pericytes - physiology
Physiology
Schizophrenia
Studies
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Summary:Cortical function is impaired in various disorders of the central nervous system including Alzheimer's disease, autism and schizophrenia. Some of these disorders are speculated to be associated with insults in early brain development. Pericytes have been shown to regulate neurovascular integrity in development, health and disease. Hence, precisely controlled mechanisms must have evolved in evolution to operate pericyte proliferation, repair and cell fate within the neurovascular unit (NVU). It is well established that pericyte deficiency leads to NVU injury resulting in cognitive decline and neuroinflammation in cortical layers. However, little is known about the role of pericytes in pathophysiological processes of the developing cortex. Here we introduce an in vitro model that enables to precisely study pericytes in the immature cortex and show that moderate inflammation and hypoxia result in caspase-3 mediated pericyte loss. Using heterozygous EYFP-NG2 mouse mutants we performed live imaging of pericytes for several days in vitro. In addition we show that pericytes maintain their capacity to proliferate which may allow cell-based therapies like reprogramming of pericytes into induced neuronal cells in the presented approach.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0081637