PMID- 32698829
OWN - NLM
STAT- MEDLINE
DCOM- 20210604
LR  - 20210604
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 17
IP  - 1
DP  - 2020 Jul 22
TI  - Muramyl dipeptide-mediated immunomodulation on monocyte subsets exerts 
      therapeutic effects in a mouse model of Alzheimer's disease.
PG  - 218
LID - 10.1186/s12974-020-01893-3 [doi]
LID - 218
AB  - BACKGROUND: 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 Ly6C(high) into Ly6C(low) monocytes. 
      Previously, we have shown that Ly6C(low) 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. METHODS: Three months old 
      APP(swe)/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. RESULTS: 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 (Abeta) elimination, respectively. 
      In addition, we found monocyte chemoattractant protein-1(MCP-1) levels 
      significantly increased, whereas intercellular adhesion molecule-1(ICAM-1) 
      significantly decreased, and microglial marker (Iba1) did not change in the 
      treatment group compared to the control. In parallel, we discovered elevated 
      cyclooxygenase-2 (COX2) expression levels in the treated group, which might be a 
      positive factor for synaptic activity. CONCLUSIONS: Our results demonstrate that 
      MDP is beneficial in both the early phase and, to some extent, later phases of 
      the pathology in the mouse model of AD. These data open the way for potential 
      MDP-based medications for AD.
FAU - Fani Maleki, Adham
AU  - Fani Maleki A
AD  - Neuroscience Laboratory, CHU de Quebec Research Center and Department of 
      Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier 
      Boulevard, Quebec City, QC, G1V 4G2, Canada.
FAU - Cisbani, Giulia
AU  - Cisbani G
AD  - Neuroscience Laboratory, CHU de Quebec Research Center and Department of 
      Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier 
      Boulevard, Quebec City, QC, G1V 4G2, Canada.
FAU - Plante, Marie-Michele
AU  - Plante MM
AD  - Neuroscience Laboratory, CHU de Quebec Research Center and Department of 
      Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier 
      Boulevard, Quebec City, QC, G1V 4G2, Canada.
FAU - Prefontaine, Paul
AU  - Prefontaine P
AD  - Neuroscience Laboratory, CHU de Quebec Research Center and Department of 
      Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier 
      Boulevard, Quebec City, QC, G1V 4G2, Canada.
FAU - Laflamme, Nataly
AU  - Laflamme N
AD  - Neuroscience Laboratory, CHU de Quebec Research Center and Department of 
      Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier 
      Boulevard, Quebec City, QC, G1V 4G2, Canada.
FAU - Gosselin, Jean
AU  - Gosselin J
AD  - Laboratory of Innate Immunity, CHU of Quebec Research Center and Department of 
      Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier 
      Boulevard, Quebec City, QC, G1V 4G2, Canada.
FAU - Rivest, Serge
AU  - Rivest S
AD  - Neuroscience Laboratory, CHU de Quebec Research Center and Department of 
      Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier 
      Boulevard, Quebec City, QC, G1V 4G2, Canada. 
      serge.rivest@crchudequebec.ulaval.ca.
LA  - eng
GR  - 331652/CIHR/
PT  - Journal Article
DEP - 20200722
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (APP protein, human)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (Presenilin-1)
RN  - 53678-77-6 (Acetylmuramyl-Alanyl-Isoglutamine)
SB  - IM
MH  - Acetylmuramyl-Alanyl-Isoglutamine/*pharmacology
MH  - *Alzheimer Disease/immunology/metabolism/pathology
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Animals
MH  - Brain/*drug effects/metabolism/pathology
MH  - Disease Models, Animal
MH  - Humans
MH  - *Immunomodulation
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Monocytes/*drug effects
MH  - Neuronal Plasticity/drug effects
MH  - Presenilin-1/genetics
PMC - PMC7376735
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Brain blood vessels
OT  - Cerebral amyloid angiopathy
OT  - Immunotherapy
OT  - Macrophages
OT  - Microglia
OT  - Monocytes
OT  - NOD2 receptor
OT  - Synapse
COIS- The authors declare that they have no competing interests.
EDAT- 2020/07/24 06:00
MHDA- 2021/06/05 06:00
PMCR- 2020/07/22
CRDT- 2020/07/24 06:00
PHST- 2020/02/26 00:00 [received]
PHST- 2020/07/13 00:00 [accepted]
PHST- 2020/07/24 06:00 [entrez]
PHST- 2020/07/24 06:00 [pubmed]
PHST- 2021/06/05 06:00 [medline]
PHST- 2020/07/22 00:00 [pmc-release]
AID - 10.1186/s12974-020-01893-3 [pii]
AID - 1893 [pii]
AID - 10.1186/s12974-020-01893-3 [doi]
PST - epublish
SO  - J Neuroinflammation. 2020 Jul 22;17(1):218. doi: 10.1186/s12974-020-01893-3.