Melatonin reduced microglial activation and alleviated neuroinflammation induced neuron degeneration in experimental traumatic brain injury: Possible involvement of mTOR pathway

Neurochem Int. 2014 Oct;76:23-31. doi: 10.1016/j.neuint.2014.06.015. Epub 2014 Jul 1.

Abstract

This study was designed to detect the modulation manner of melatonin on microglial activation and explore herein possible involvement of mammalian target of rapamycin (mTOR) pathway following traumatic brain injury (TBI). ICR mice were divided into four groups: sham group, TBI group, TBI+sal group and TBI+Melatonin group. A weight-drop model was employed to cause TBI. Neurological severity score (NSS) tests were performed to measure behavioral outcomes. Nissl staining was conducted to observe the neuronal degeneration and wet-to-dry weight ratio indicated brain water content. Immunofluorescence was designed to investigate microglial activation. Enzyme-linked immunosorbent assay (ELISA) was employed to evaluate proinflammatory cytokine levels (interleukin-beta (IL-1β), tumor necrosis factor-alpha (TNF-α)). Western blotting was engaged to analyze the protein content of mammalian target of rapamycin (mTOR), p70 ribosomal S6 kinase (p70S6K) and S6 ribosomal protein (S6RP). Melatonin administration was associated with markedly restrained microglial activation, decreased release of proinflammatory cytokines and increased the number of surviving neurons at the site of peri-contusion. Meanwhile, melatonin administration resulted in dephosphorylated mTOR pathway. In conclusion, this study presents a new insight into the mechanisms responsible for the anti-neuroinflammation of melatonin, with possible involvement of mTOR pathway.

Keywords: Inflammation; Mammalian target of rapamycin; Melatonin; Microglia activation; Traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Blotting, Western
  • Brain Injuries / metabolism
  • Brain Injuries / pathology*
  • Brain Injuries / physiopathology
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Inflammation / physiopathology
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism
  • Male
  • Melatonin / pharmacology*
  • Mice
  • Mice, Inbred ICR
  • Microglia / drug effects*
  • Neurons / pathology*
  • TOR Serine-Threonine Kinases / physiology*

Substances

  • Inflammation Mediators
  • TOR Serine-Threonine Kinases
  • Melatonin