Genetic defects disrupting glial ion and water homeostasis in the brain

Rogier Min*, Marjo S. van der Knaap

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Electrical activity of neurons in the brain, caused by the movement of ions between intracellular and extracellular compartments, is the basis of all our thoughts and actions. Maintaining the correct ionic concentration gradients is therefore crucial for brain functioning. Ion fluxes are accompanied by the displacement of osmotically obliged water. Since even minor brain swelling leads to severe brain damage and even death, brain ion and water movement has to be tightly regulated. Glial cells, in particular astrocytes, play a key role in ion and water homeostasis. They are endowed with specific channels, pumps and carriers to regulate ion and water flow. Glial cells form a large panglial syncytium to aid the uptake and dispersal of ions and water, and make extensive contacts with brain fluid barriers for disposal of excess ions and water. Genetic defects in glial proteins involved in ion and water homeostasis disrupt brain functioning, thereby leading to neurological diseases. Since white matter edema is often a hallmark disease feature, many of these diseases are characterized as leukodystrophies. In this review we summarize our current understanding of inherited glial diseases characterized by disturbed brain ion and water homeostasis by integrating findings from MRI, genetics, neuropathology and animal models for disease. We discuss how mutations in different glial proteins lead to disease, and highlight the similarities and differences between these diseases. To come to effective therapies for this group of diseases, a better mechanistic understanding of how glial cells shape ion and water movement in the brain is crucial.

Original languageEnglish
Pages (from-to)372-387
Number of pages16
JournalBrain Pathology
Volume28
Issue number3
Early online date8 May 2018
DOIs
Publication statusPublished - May 2018

    Fingerprint

Keywords

  • astrocytes
  • homeostasis
  • leukodystrophies
  • oligodendrocytes
  • panglial syncytium

Cite this