Glial cells as key elements in the pathophysiology and treatment of bipolar disorder

Acta Neuropsychiatr. 2017 Jun;29(3):140-152. doi: 10.1017/neu.2016.56. Epub 2016 Oct 24.

Abstract

Objective: The exact pathophysiology of bipolar disorder (BD) is not yet fully understood, and there are many questions in this area which should be answered. This review aims to discuss the roles of glial cells in the pathophysiology of BD and their contribution to the mechanism of action of mood-stabilising drugs.

Methods: We critically reviewed the most recent advances regarding glial cell roles in the pathophysiology and treatment of BD and the neuroprotective and neurotrophic effects of these cells.

Results: Postmortem studies revealed a decrease in the glial cell number or density in the specific layers of prefrontal and anterior cingulate cortex in the patients with BD, whereas there was no difference in other brain regions, such as entorhinal cortex, amygdala and hippocampus. Astrocytes and oligodendrocytes were the most important glial types that were responsible for the glial reduction, but microglia activation rather than loss may be implicated in BD. The decreased number or density of glial cells may contribute to the pathological changes observed in neurons in the patients with BD. Alteration of specific neurotrophic factors such as glial cell line-derived neurotrophic factor and S100B may be an important feature of BD. Glial cells mediate the therapeutic effects of mood-stabilising agents in the treatment of BD.

Conclusion: Recent studies provide important evidence on the impairment of glial cells in the pathophysiology and treatment of BD. However, future controlled studies are necessary to elucidate different aspects of glial cells contribution to BD, and the mechanism of action of mood-stabilising drugs.

Keywords: S100B; bipolar disorder; glial cell line-derived neurotrophic factor; glial cells; mood-stabilising drugs.

Publication types

  • Review

MeSH terms

  • Amygdala / cytology*
  • Amygdala / metabolism
  • Amygdala / pathology
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / physiopathology*
  • Brain / pathology
  • Brain / physiopathology
  • Diagnosis
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Hippocampus / cytology*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Mood Disorders / drug therapy
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Neuroglia / physiology*
  • Neurons / metabolism
  • Neurons / pathology
  • Oligodendroglia / metabolism
  • Oligodendroglia / pathology
  • S100 Calcium Binding Protein beta Subunit / metabolism

Substances

  • GDNF protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human