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Related Experiment Video

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Purification of Mouse Brain Vessels
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Mlc1-Expressing Perivascular Astrocytes Promote Blood-Brain Barrier Integrity.

John E Morales1, Arpan De1, Alexandra A Miller1

  • 1Department of Neurosurgery and Brain Tumor Center, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|December 30, 2021
PubMed
Summary

Perivascular astrocytes (PAs) are crucial for maintaining the blood-brain barrier (BBB) integrity. Ablating these cells causes BBB defects, leading to premature death and neurological issues.

Keywords:
angiogenesisendothelial celljuxtavascularmegalencephalic leukoencephalopathy with subcortical cysts 1microenvironmentneurovascular

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Vascular Biology

Background:

  • Perivascular astrocytes (PAs) are strategically positioned near brain blood vessels.
  • Their specific roles in blood-brain barrier (BBB) regulation are not fully understood due to challenges in distinguishing them from other astrocytes.
  • The megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1) gene is implicated in astrocyte function.

Purpose of the Study:

  • To develop a novel mouse model for selective identification and manipulation of PAs in vivo.
  • To investigate the essential functions of PAs in maintaining BBB integrity.
  • To explore the consequences of PA loss on endothelial cell junctions and brain pathology.

Main Methods:

  • Generation of a knock-in mouse model (MLCT) using Mlc1-T2A-CreERT2 for targeted PA identification and tracking.
  • MLCT-mediated ablation of PAs to study their in vivo functions.
  • Assessment of BBB integrity, endothelial cell junctional protein localization (Claudin 5, VE-Cadherin), and microgliosis.

Main Results:

  • The MLCT mouse model enables selective identification and tracking of PAs.
  • Ablation of PAs leads to severe BBB integrity defects and premature mortality.
  • PA loss results in aberrant Claudin 5 and VE-Cadherin localization and significant microgliosis.

Conclusions:

  • Mlc1-expressing PAs play essential roles in regulating endothelial barrier integrity in the mouse brain.
  • Primary astrocyte defects causing BBB breakdown may contribute to human neurological disorders.
  • This study highlights PAs as critical regulators of neurovascular function.