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Impact of Aging in Microglia-Mediated D-Serine Balance in the CNS

Sebastián Beltrán-Castillo1, Jaime Eugenín2, Rommy von Bernhardi1

  • 1Departamento de Neurología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.

Mediators of Inflammation
|October 27, 2018
PubMed

Insights

Aging brains exhibit chronic inflammation, impairing microglia and increasing D-serine. This age-related D-serine dysregulation contributes to neuroinflammation, cognitive decline, and neurodegenerative diseases like Alzheimer's.

Area of Science:

  • Neuroscience
  • Immunology
  • Gerontology

Background:

  • Aging is associated with a chronic, low-grade inflammatory state.
  • This neuroinflammation affects microglial function, shifting them towards a pro-inflammatory and cytotoxic phenotype.
  • Dysfunctional microglia fail in their neuroprotective roles and exacerbate brain damage.

Purpose of the Study:

  • To investigate the impact of the age-dependent inflammatory brain environment on D-serine levels and its regulation by microglia.
  • To explore the role of microglia-mediated D-serine dysregulation in glutamatergic transmission.
  • To understand how D-serine dysregulation contributes to cognitive impairment and neurodegeneration.

Main Methods:

  • The study focuses on the functional changes in microglia during aging.
  • It examines the link between microglial inflammatory activation and D-serine release.
  • Investigates the consequences of D-serine dysregulation on glutamatergic transmission, synaptogenesis, synaptic plasticity, and excitotoxicity.

Main Results:

  • Inflammatory activation of microglia leads to increased D-serine release.
  • Age-dependent inflammatory conditions promote microglia-mediated alterations in D-serine-regulated glutamatergic transmission.
  • D-serine dysregulation impacts synaptogenesis, synaptic plasticity, and potentiates NMDAR-dependent excitotoxicity.

Conclusions:

  • Microglia-mediated D-serine dysregulation plays a significant role in age-related cognitive impairment.
  • This dysregulation may contribute to the induction and progression of neurodegenerative diseases, including Alzheimer's disease.
  • Targeting microglial function and D-serine pathways could offer therapeutic strategies for age-related neurological disorders.

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