Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin/TLR4/MyD88/NF-κB-Mediated Neuroinflammation...

Area of Science:

• Neuroscience
• Endocrinology
• Cell Biology

Background:

• Neuroinflammation is a key characteristic of type 2 diabetes mellitus (T2DM), negatively impacting hippocampal neurogenesis and cognitive function.
• The underlying mechanisms are not fully elucidated, and effective therapeutic strategies remain limited.

Purpose of the Study:

• To investigate the effects of exercise on neuroinflammation and hippocampal neurogenesis in T2DM mice.
• To clarify the role of the irisin signaling pathway in mediating the benefits of exercise in T2DM.

Main Methods:

• Ten-week exercise intervention in T2DM mice.
• Administration of cyclo RGDyk, an irisin receptor signaling inhibitor.
• Assessment of hippocampal neuroinflammation, neurogenesis, microglial polarization (M1 phenotype), and key signaling molecules (FNDC5/irisin, TLR4, MyD88, NF-κB).

Main Results:

• Exercise significantly reduced inflammation, promoted hippocampal neurogenesis and memory function in T2DM mice.
• These benefits were reversed by irisin receptor inhibition.
• Exercise decreased M1 microglia polarization and modulated the irisin/TLR4/MyD88/NF-κB pathway, effects blunted by irisin receptor blockade.

Conclusions:

• Exercise ameliorates T2DM-induced neuroinflammation and cognitive deficits.
• The beneficial effects are mediated through the irisin/TLR4/MyD88/NF-κB signaling pathway.
• Exercise holds potential for managing cognitive decline associated with diabetes.