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

PLoS One. 2013 Nov 21;8(11):e81637. doi: 10.1371/journal.pone.0081637. eCollection 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • Cell Hypoxia
  • Cell Proliferation
  • Cell Survival
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / enzymology
  • Cerebral Cortex / growth & development*
  • Inflammation / enzymology
  • Mice
  • Mice, Inbred C57BL
  • Pericytes / cytology
  • Pericytes / physiology*

Substances

  • Caspase 3

Grants and funding

CMZ was supported by a Stage 1 grant of the University Medical Center of the Johannes Gutenberg-University of Mainz. This work was supported by DFG grants to HJL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.