Microglia enhance neurogenesis and oligodendrogenesis in the early postnatal subventricular zone

Yukari Shigemoto-Mogami1, Kazue Hoshikawa, James E Goldman

  • 1Laboratory of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, Tokyo 158-8501, Japan, and Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032.

Insights

Activated microglia in the developing brain enhance neural stem cell proliferation. Suppressing these immune cells and their inflammatory cytokines reduced neurogenesis and oligodendrogenesis.

Area of Science:

  • Neuroscience
  • Immunology
  • Developmental Biology

Background:

  • Microglia are traditionally viewed as brain immune cells.
  • Emerging evidence highlights their physiological roles in normal central nervous system (CNS) development.

Purpose of the Study:

  • To investigate the role of activated microglia in the developing rat brain.
  • To determine the impact of microglia-derived cytokines on neurogenesis and oligodendrogenesis.

Main Methods:

  • Identified and quantified activated microglia in the rat forebrain subventricular zone (SVZ) from postnatal day 1 to 10.
  • Used pharmacological agents to suppress microglial activation and measured changes in proinflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ).
  • Conducted in vitro neurosphere assays to assess the direct effects of activated microglia and cytokines on neurogenesis and oligodendrogenesis.

Main Results:

  • Large numbers of activated microglia were found in the early postnatal SVZ.
  • Pharmacological suppression of microglia significantly inhibited neurogenesis and oligodendrogenesis.
  • In vitro assays confirmed that activated microglia and their secreted cytokines enhance neurogenesis and oligodendrogenesis.

Conclusions:

  • Activated microglia accumulate in the early postnatal SVZ.
  • These microglia promote neurogenesis and oligodendrogenesis through the release of cytokines.
  • Microglia play a crucial physiological role in CNS development.