sTREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K-AKT signaling pathway

Area of Science:

• Neuroimmunology
• Molecular Biology
• Neuroinflammation

Background:

• Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is elevated in neuropsychiatric systemic lupus erythematosus (NPSLE).
• The precise mechanisms by which sTREM-1 contributes to brain damage in NPSLE remain largely unknown.
• Understanding sTREM-1's role is crucial for developing targeted therapies for neurological complications.

Purpose of the Study:

• To investigate the role of sTREM-1 in inducing hippocampal damage.
• To elucidate the underlying molecular mechanisms of sTREM-1-mediated neuroinflammation.
• To evaluate the therapeutic potential of targeting the sTREM-1 pathway.

Main Methods:

• Intracerebroventricular (ICV) injection of sTREM-1 recombinant protein in C57BL/6 mice.
• In vitro stimulation of BV2 microglial cells with sTREM-1.
• Assessment of neuronal damage, microglial activation and polarization, apoptosis, and phagocytosis.
• Pharmacological inhibition of the PI3K-AKT signaling pathway using LY294002.

Main Results:

• ICV injection of sTREM-1 increased hippocampal neuronal damage, synaptic loss, and microglial activation.
• In vitro, sTREM-1 reduced BV2 cell apoptosis, promoted M1 polarization, and enhanced phagocytic activity.
• sTREM-1 activated the PI3K-AKT signaling pathway, which was reversed by LY294002, improving hippocampal damage.
• Microglial activation and excessive phagocytosis of neuronal synapses by sTREM-1 were mediated by the PI3K-AKT pathway.

Conclusions:

• sTREM-1 induces hippocampal damage by activating microglia through the PI3K-AKT pathway.
• This activation leads to excessive phagocytosis of neuronal synapses, contributing to neuroinflammation and neuronal injury.
• sTREM-1 represents a potential therapeutic target for mitigating brain lesions in conditions like NPSLE.