Muramyl dipeptide-mediated immunomodulation on monocyte subsets exerts therapeutic effects in a mouse model of Alzheimer's disease.

Journal of Neuroinflammation
Adham Fani MalekiSerge Rivest

Abstract

Muramyl dipeptide (MDP) is a component derived from minimal peptidoglycan motif from bacteria, and it is a ligand for the NOD2 receptor. Peripheral administration of MDP converts Ly6Chigh into Ly6Clow monocytes. Previously, we have shown that Ly6Clow monocytes play crucial roles in the pathology of a mouse model of Alzheimer's disease (AD). However, medications with mild immunomodulatory effects that solely target specific monocyte subsets, without triggering microglial activation, are rare. Three months old APPswe/PS1 transgenic male mice and age-matched C57BL/6 J mice were used for high frequency (2 times/week) over 6 months and low frequency (once a week) over 3 months of intraperitoneally MDP (10 mg/kg) administrations. Flow cytometry analysis of monocyte subsets in blood, and behavioral and postmortem analyses were performed. Memory tests showed mild to a strong improvement in memory function, increased expression levels of postsynaptic density protein 95 (PSD95), and low-density lipoprotein receptor-related protein 1 (LRP1), which are involved in synaptic plasticity and amyloid-beta (Aβ) elimination, respectively. In addition, we found monocyte chemoattractant protein-1(MCP-1) levels significantly increased, whereas inter...Continue Reading

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Citations

Dec 3, 2020·International Journal of Molecular Sciences·Anna ChiariniIlaria Dal Prà
Jan 23, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Adham Fani MalekiSerge Rivest
Nov 17, 2020·Frontiers in Neurology·Joohyun ParkJong Eun Lee
Mar 3, 2021·European Journal of Medicinal Chemistry·Sukriti SrivastavaSunil Kumar Khare
Apr 16, 2021·Molecular Psychiatry·Giulia Cisbani, Serge Rivest
Aug 4, 2021·Brain, Behavior, and Immunity·Mohammed A Al-OnaiziAyman ElAli

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Methods Mentioned

BETA
PCR
fluorescence-activated cell sorting
flow cytometry
ELISA

Software Mentioned

Stereo Investigator
Zen
FACSDiva
Adobe Photoshop CS5
Pierce myImage Analysis
GraphPad
Adobe Illustrator CS5
SAS
GraphPad Prism

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