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Melatonin prevents diabetes-associated cognitive dysfunction from microglia-mediated neuroinflammation by activating

Yixin Cui1,2, Mengmeng Yang1,2, Yilin Wang3

  • 1Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|March 12, 2021
PubMed

Insights

Melatonin (MLT) treatment improved learning and memory in diabetic mice by activating autophagy. This process reduced neuroinflammation and microglial apoptosis through the toll-like receptor 4 (TLR4)/Akt/mTOR pathway.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Cell Biology

Background:

  • Diabetes mellitus is frequently associated with cognitive dysfunction.
  • Neuroinflammation and microglial apoptosis contribute to diabetes-related cognitive decline.

Purpose of the Study:

  • To investigate the efficacy of melatonin (MLT) in ameliorating cognitive deficits in type 2 diabetic mice.
  • To elucidate the underlying mechanisms, focusing on autophagy and the TLR4/Akt/mTOR pathway.

Main Methods:

  • Type 2 diabetic mice and palmitic acid (PA)-stimulated BV-2 microglial cells were treated with MLT.
  • Cognitive function was assessed using the Morris water maze test.
  • Neuroinflammation, microglial apoptosis, and key signaling pathway components (TLR4, Akt, mTOR) were analyzed.

Main Results:

  • MLT treatment significantly improved learning and memory impairments in diabetic mice.
  • MLT administration reduced neuroinflammation and microglial apoptosis.
  • Autophagy activation by MLT was confirmed, as an autophagy inhibitor reversed MLT's beneficial effects.
  • MLT treatment downregulated TLR4, phosphorylated-Akt, and phosphorylated-mTOR levels.

Conclusions:

  • Melatonin effectively improves cognitive function in type 2 diabetic mice.
  • The therapeutic effects of MLT are mediated by autophagy activation.
  • MLT exerts anti-inflammatory and anti-apoptotic effects by inhibiting the TLR4/Akt/mTOR pathway.
Keywords:
apoptosisautophagycognitionmelatoninneuroinflammation

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