Granulocyte-macrophage colony-stimulating factor neuroprotective activities in Alzheimer's disease mice

J Neuroimmunol. 2018 Jun 15:319:80-92. doi: 10.1016/j.jneuroim.2018.03.009. Epub 2018 Mar 17.

Abstract

We investigated the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on behavioral and pathological outcomes in Alzheimer's disease (AD) and non-transgenic mice. GM-CSF treatment in AD mice reduced brain amyloidosis, increased plasma Aβ, and rescued cognitive impairment with increased hippocampal expression of calbindin and synaptophysin and increased levels of doublecortin-positive cells in the dentate gyrus. These data extend GM-CSF pleiotropic neuroprotection mechanisms in AD and include regulatory T cell-mediated immunomodulation of microglial function, Aβ clearance, maintenance of synaptic integrity, and induction of neurogenesis. Together these data support further development of GM-CSF as a neuroprotective agent for AD.

Keywords: APP/PS1 mice; Amyloidosis; Aβ plaques; Calbindin; Cognitive function; Doublecortin; Hippocampus; Synaptophysin; Tregs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Alzheimer Disease* / physiopathology
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Mice
  • Mice, Transgenic
  • Neuroprotective Agents / pharmacology*

Substances

  • Neuroprotective Agents
  • Granulocyte-Macrophage Colony-Stimulating Factor