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Acute glucose fluctuation impacts microglial activity, leading to inflammatory activation or self-degradation

Cheng-Fang Hsieh1,2,3, Ching-Kuan Liu1,2, Ching-Tien Lee4

  • 1Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Scientific Reports
|January 31, 2019
PubMed

Insights

Acute glucose fluctuations in diabetes mellitus significantly impact brain microglial cells. These changes can lead to inflammation or self-degradation, contributing to neurodegeneration and cognitive decline in diabetic patients.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Immunology

Background:

  • Diabetes mellitus is linked to a higher risk of Alzheimer's dementia and cognitive decline.
  • The precise mechanisms driving neurodegeneration in diabetic patients are not fully understood.
  • Alterations in microglial activity, influenced by blood sugar variability, are a potential etiological factor.

Purpose of the Study:

  • To investigate the effects of acute fluctuations in ambient glucose levels on BV-2 microglial cell activity.
  • To elucidate the molecular pathways involved in glucose fluctuation-induced microglial stress responses.

Main Methods:

  • Exposure of BV-2 microglial cells to shifts between normal glucose (NG) and high glucose (HG) conditions.
  • Assay of biochemical parameters, including cell viability (MTT reduction), oxidative stress markers, inflammatory cytokine secretion (TNF-α), and protein expression (HSP70, HO-1, iNOS, COX-2).
  • Assessment of apoptosis and autophagy markers (Bcl-2, cleaved caspase-3, TUNEL, LC3B-II) and analysis of signaling pathways (MAPKs, PI3K/Akt, NF-κB).

Main Results:

  • A shift from NG to HG increased microglial growth, oxidative/inflammatory stress, and activation, amplifying LPS-induced inflammation.
  • A shift from HG to NG induced metabolic stress, apoptosis, and autophagy in microglia.
  • These effects were mediated by the activation of MAPKs, PI3K/Akt, and NF-κB signaling pathways.

Conclusions:

  • Acute glucose fluctuations induce significant stress in microglia, leading to either inflammatory activation or self-degradation.
  • These altered microglial responses represent a novel pathogenic mechanism contributing to neurological deterioration in diabetes.
  • Understanding these mechanisms may offer new therapeutic targets for preventing cognitive decline in diabetic individuals.

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