Persistent Acidic Environment Induces Impaired Phagocytosis via ERK in Microglia

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Acidic environments are present in neurological disorders like stroke and Alzheimer's disease.
• Microglial functional changes in acidic conditions are not well understood.
• Microglia play crucial roles in central nervous system (CNS) immunity and homeostasis.

Purpose of the Study:

• To investigate the mechanisms underlying microglial functional changes in acidic environments.
• To explore the role of extracellular signal-regulated kinase (ERK) signaling in acid-induced microglial dysfunction.
• To identify potential therapeutic targets for restoring microglial function in CNS acidic conditions.

Main Methods:

• BV2 cells and primary neonatal microglia were exposed to acidic stimuli (pH 6.8).
• Gene expression (mRNA levels of IL-1β, IL-6, IL-10, TGF-β1, Cx3cr1, P2ry12, TDAG8) and protein levels (cAMP, PKA, p-ERK) were analyzed.
• Phagocytic function was assessed.
• The effect of ERK inhibitor (FR 180,204) was evaluated.

Main Results:

• Acidic stimuli altered the expression of inflammatory and homeostatic genes in microglia.
• Persistent acidic exposure impaired microglial phagocytic function.
• ERK signaling pathway was modulated by acidic conditions, with inhibition during short-term and activation during persistent exposure.
• ERK inhibition rescued acid-induced microglial dysfunction.

Conclusions:

• Acidic environments induce significant functional and molecular changes in microglia.
• ERK signaling plays a critical role in mediating microglial dysfunction under persistent acidic conditions.
• Targeting ERK signaling presents a potential therapeutic strategy for neurological disorders associated with CNS acidity.