PMID- 32457323
OWN - NLM
STAT- MEDLINE
DCOM- 20201211
LR  - 20231111
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 May 26
TI  - A 3'UTR modification of the TNF-alpha mouse gene increases peripheral TNF-alpha and 
      modulates the Alzheimer-like phenotype in 5XFAD mice.
PG  - 8670
LID - 10.1038/s41598-020-65378-2 [doi]
LID - 8670
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine, involved in 
      Alzheimer's disease pathogenesis. Anti-TNF-alpha therapeutic approaches currently 
      used in autoimmune diseases have been proposed as a therapeutic strategy in AD. 
      We have previously examined the role of TNF-alpha and anti-TNF-alpha drugs in AD, using 
      5XFAD mice, and we have found a significant role for peripheral TNF-alpha in brain 
      inflammation. Here we investigated the role of mouse TNF-alpha on the AD-like 
      phenotype of 5XFAD mice using a knock-in mouse with deletion of the 3'UTR of the 
      endogenous TNF-alpha (TNF(DeltaARE/+)) that develops rheumatoid arthritis and Crohn's 
      disease. 5XFAD/TNF(DeltaARE/+) mice showed significantly decreased amyloid 
      deposition. Interestingly, microglia but not astrocytes were activated in 5XFAD/ 
      TNF(DeltaARE/+) brains. This microglial activation was associated with increased 
      infiltrating peripheral leukocytes and perivascular macrophages and synaptic 
      degeneration. APP levels and APP processing enzymes involved in Abeta production 
      remained unchanged, suggesting that the reduced amyloid burden can be attributed 
      to the increased microglial and perivascular macrophage activation caused by 
      TNF-alpha. Peripheral TNF-alpha levels were increased while brain TNF-alpha remained the 
      same. These data provide further evidence for peripheral TNF-alpha as a mediator of 
      inflammation between the periphery and the brain.
FAU - Kalovyrna, Nikoleta
AU  - Kalovyrna N
AD  - Laboratory of Cellular Neurobiology, Center of Basic Research, Biomedical 
      Research Foundation, Academy of Athens, 11527, Athens, Greece.
FAU - Apokotou, Olympia
AU  - Apokotou O
AD  - Laboratory of Cellular Neurobiology, Center of Basic Research, Biomedical 
      Research Foundation, Academy of Athens, 11527, Athens, Greece.
FAU - Boulekou, Sotiria
AU  - Boulekou S
AD  - Laboratory of Cellular Neurobiology, Center of Basic Research, Biomedical 
      Research Foundation, Academy of Athens, 11527, Athens, Greece.
FAU - Paouri, Evi
AU  - Paouri E
AD  - Laboratory of Cellular Neurobiology, Center of Basic Research, Biomedical 
      Research Foundation, Academy of Athens, 11527, Athens, Greece.
FAU - Boutou, Athena
AU  - Boutou A
AD  - Laboratory of Cellular Neurobiology, Center of Basic Research, Biomedical 
      Research Foundation, Academy of Athens, 11527, Athens, Greece.
FAU - Georgopoulos, Spiros
AU  - Georgopoulos S
AD  - Laboratory of Cellular Neurobiology, Center of Basic Research, Biomedical 
      Research Foundation, Academy of Athens, 11527, Athens, Greece. 
      sgeorgopoulos@bioacademy.gr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200526
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - 3' Untranslated Regions/*genetics
MH  - Alzheimer Disease/genetics/*pathology
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Arthritis, Rheumatoid/genetics
MH  - Brain/pathology
MH  - Crohn Disease/genetics
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Knock-In Techniques
MH  - Macrophage Activation/immunology
MH  - Macrophages/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microglia/metabolism
MH  - Plaque, Amyloid/*pathology
MH  - Tumor Necrosis Factor-alpha/*genetics/metabolism
PMC - PMC7250826
COIS- The authors declare no competing interests.
EDAT- 2020/05/28 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/05/26
CRDT- 2020/05/28 06:00
PHST- 2019/12/03 00:00 [received]
PHST- 2020/04/28 00:00 [accepted]
PHST- 2020/05/28 06:00 [entrez]
PHST- 2020/05/28 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/05/26 00:00 [pmc-release]
AID - 10.1038/s41598-020-65378-2 [pii]
AID - 65378 [pii]
AID - 10.1038/s41598-020-65378-2 [doi]
PST - epublish
SO  - Sci Rep. 2020 May 26;10(1):8670. doi: 10.1038/s41598-020-65378-2.