Magnesium Ion Reduces Neuroinflammation By Suppressing The Expression Of Interleukin-1β In The Brain Of APP/PS1 Transgenic Mouse

Alzheimer ’s disease(AD)is a neurodegenerative disorder characterized pathologically by the accumulation of β-amyloid protein(Aβ)and the presence of neurofibrillary tangles(NFTs)in the brain.AD is recently identified to be associated with magnesium ion(Mg2+)deficit and interleukin-1β(IL-1β)elevation in the serum or brain of AD patients.However,the mechanisms regulating IL-1β expression by Mg2+ dyshomeostasis in the pathological condition of AD remain unknown We have explored whether and how Mg2+ reduces neuroinflammation of APP/PS1 transgenic mouse by suppressing the expression of IL-1β.We herein studied the mechanism of IL-1β reduction by a recently developed compound,magnesium-L-threonate(MgT)treatment.Using human glioblastoma A172 and mouse brain D1A glial cells as an in vitro model system,we delineated the mechanism by which MgT suppressed the expression of IL-1β in glial cells.In detail,we found that MgT incubation stimulated the activity of ERK1/2 and PPARγ signaling pathways by phosphorylation,which resulted in IL-1β expression.Simultaneous inhibiting the phosphorylation of ERK1/2 and PPARγ resulted in IL-1β upregulation in MgT-stimulated glial cells.In line with our in vitro data,intracerebroventricula injection(i.c.v)of MgT to the ventricles of APP/PS1 transgenic mice or treatment of APP/PS1 brain slices suppressed the mRNA and protein expression of IL-1β.These in vivo observations were further supported by oral administration of MgT for 5 months.More importantly,Mg2+ influx into the ventricles of mice blocked the effects of IL-1βor Aβ oligomers in cerebrospinal fluid(CSF)on stimulating the expression of IL-1βin cerebral cortex of APP/PS1 transgenic mice.Our study reveals Mg2+ reduces neuroinflammation of APP/PS1 transgenic mice by suppressing the expression of IL-1β.