title: Magnesium ion influx reduces neuroinflammation in Aβ precursor protein/Presenilin 1 transgenic mice by suppressing the expression of interleukin-1β.
abstract: Alzheimer's disease (AD) has been associated with magnesium ion (Mg2+) deficits and interleukin-1β (IL-1β) elevations in the serum or brains of AD patients. However, the mechanisms regulating IL-1β expression during Mg2+dyshomeostasis in AD remain unknown. We herein studied the mechanism of IL-1β reduction using a recently developed compound, magnesium-L-threonate (MgT). Using human glioblastoma A172 and mouse brain D1A glial cells as an in vitro model system, we delineated the signaling pathways by which MgT suppressed the expression of IL-1β in glial cells. In detail, we found that MgT incubation stimulated the activity of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathways by phosphorylation, which resulted in IL-1β suppression. Simultaneous inhibition of the phosphorylation of ERK1/2 and PPARγ induced IL-1β upregulation in MgT-stimulated glial cells. In accordance with our in vitro data, the intracerebroventricular (i.c.v) injection of MgT into the ventricles of APP/PS1 transgenic mice and treatment of Aβ precursor protein (APP)/PS1 brain slices suppressed the mRNA and protein expression of IL-1β. These in vivo observations were further supported by the oral administration of MgT for 5 months. Importantly, Mg2+influx into the ventricles of the mice blocked the effects of IL-1β or amyloid β-protein oligomers in the cerebrospinal fluid. This reduced the stimulation of IL-1β expression in the cerebral cortex of APP/PS1 transgenic mice, which potentially contributed to the inhibition of neuroinflammation.
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang, P. R. China.
authors.forename: Pu
authors.initials: P
authors.lastname: Wang
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang, P. R. China.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Guan
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang, P. R. China.
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Guo
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang, P. R. China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhao
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang, P. R. China.
authors.forename: Zhan-You
authors.initials: ZY
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D053764:Presenilin-1 / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053583:Interleukin-1beta; D053764:Presenilin-1; D008274:Magnesium