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

Tomomi Kiyota; Jatin Machhi; Yaman Lu; Bhagyalaxmi Dyavarshetty; Maryam Nemati; Izumi Yokoyama; R. Lee Mosley; Howard E. Gendelman

doi:10.1016/j.jneuroim.2018.03.009

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

Tomomi Kiyota, Jatin Machhi, Yaman Lu, Bhagyalaxmi Dyavarshetty, Maryam Nemati, Izumi Yokoyama, R. Lee Mosley, Howard E. Gendelman

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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.

Original language	English (US)
Pages (from-to)	80-92
Number of pages	13
Journal	Journal of Neuroimmunology
Volume	319
DOIs	https://doi.org/10.1016/j.jneuroim.2018.03.009
State	Published - Jun 15 2018

Keywords

APP/PS1 mice
Amyloidosis
Aβ plaques
Calbindin
Cognitive function
Doublecortin
Hippocampus
Synaptophysin
Tregs

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Neurology
Clinical Neurology

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10.1016/j.jneuroim.2018.03.009

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Granulocyte-macrophage colony-stimulating factor neuroprotective activities in Alzheimer's disease mice. / Kiyota, Tomomi; Machhi, Jatin; Lu, Yaman; Dyavarshetty, Bhagyalaxmi; Nemati, Maryam; Yokoyama, Izumi; Lee Mosley, R.; Gendelman, Howard E.

In: Journal of Neuroimmunology, Vol. 319, 15.06.2018, p. 80-92.

Research output: Contribution to journal › Article › peer-review

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title = "Granulocyte-macrophage colony-stimulating factor neuroprotective activities in Alzheimer's disease mice",

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",

author = "Tomomi Kiyota and Jatin Machhi and Yaman Lu and Bhagyalaxmi Dyavarshetty and Maryam Nemati and Izumi Yokoyama and {Lee Mosley}, R. and Gendelman, {Howard E.}",

note = "Funding Information: This work was supported in part by NIH Grant AG043540 , DA028555 , NS036126 , NS034239 , MH064570 , NS043985 , MH062261 , and DOD Grant 421–20-09 A to HEG, the Carol Swarts Emerging Neuroscience Fund, start-up funds from the Department of Pharmacology and Experimental Neuroscience, and the Shoemaker Award for Neurodegenerative Research to TK. Funding Information: This work was supported in part by NIH Grant AG043540, DA028555, NS036126, NS034239, MH064570, NS043985, MH062261, and DOD Grant 421–20-09A to HEG, the Carol Swarts Emerging Neuroscience Fund, start-up funds from the Department of Pharmacology and Experimental Neuroscience, and the Shoemaker Award for Neurodegenerative Research to TK. Publisher Copyright: {\textcopyright} 2018 Elsevier B.V.",

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AU - Nemati, Maryam

AU - Yokoyama, Izumi

AU - Lee Mosley, R.

AU - Gendelman, Howard E.

N1 - Funding Information: This work was supported in part by NIH Grant AG043540 , DA028555 , NS036126 , NS034239 , MH064570 , NS043985 , MH062261 , and DOD Grant 421–20-09 A to HEG, the Carol Swarts Emerging Neuroscience Fund, start-up funds from the Department of Pharmacology and Experimental Neuroscience, and the Shoemaker Award for Neurodegenerative Research to TK. Funding Information: This work was supported in part by NIH Grant AG043540, DA028555, NS036126, NS034239, MH064570, NS043985, MH062261, and DOD Grant 421–20-09A to HEG, the Carol Swarts Emerging Neuroscience Fund, start-up funds from the Department of Pharmacology and Experimental Neuroscience, and the Shoemaker Award for Neurodegenerative Research to TK. Publisher Copyright: © 2018 Elsevier B.V.

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N2 - 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.

AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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