Disruption of oligodendrocyte progenitor cells is an early sign of pathology in the triple transgenic mouse model of Alzheimer’s disease

Ilaria Vanzulli, Maria Papanikolaou, Irene Chacon De La Rocha, Andrea Rivera, Diego Gomez-Nicola, Alexei Verkhratsky, Jose J. Rodriguez, Arthur Butt

Research output: Contribution to journalArticlepeer-review

17 Downloads (Pure)

Abstract

There is increasing evidence that myelin disruption is related to cognitive decline in Alzheimer's disease (AD). In the CNS, myelin is produced by oligodendrocytes, which are generated throughout life by adult oligodendrocyte progenitor cells (OPCs), also known as NG2-glia. To address whether alterations in myelination are related to age-dependent changes in OPCs, we analyzed NG2 and myelin basic protein (MBP) immunolabelling in the hippocampus of 3×Tg-AD mice at 6 and 24 months of age, compared with non-Tg age-matched controls. There was an age-related decrease in MBP immunostaining and OPC density, together with a decline in the number of OPC sister cells, a measure of OPC replication. Notably, the loss of myelin and OPC sister cells occurred earlier at 6 months in 3xTg-AD, suggesting accelerated aging, although there was not a concomitant decline in OPC numbers at this age, suggesting the observed changes in myelin were not a consequence of replicative exhaustion, but possibly of OPC disruption or senescence. In line with this, a key finding is that compared to age-match controls, OPC displayed marked morphological atrophy at 6 months in 3xTg-AD followed by morphological hypertrophy at 24 months, as deduced from significant changes in total cell surface area, total cell volume, somata volume and branching of main processes. Moreover, we show that hypertrophic OPCs surround and infiltrate amyloid-β (Aβ) plaques, a key pathological hallmark of AD. The results indicate that OPCs undergo complex age-related remodeling in the hippocampus of the 3xTg-AD mouse model. We conclude that OPC disruption is an early pathological sign in AD and is a potential factor in accelerated myelin loss and cognitive decline.
Original languageEnglish
Pages (from-to)130-139
JournalNeurobiology of Aging
Volume94
Early online date7 Jun 2020
DOIs
Publication statusPublished - 1 Oct 2020

Keywords

  • RCUK
  • BBSRC
  • MRC
  • BB/M029379/1
  • MR/P025811/1

Fingerprint

Dive into the research topics of 'Disruption of oligodendrocyte progenitor cells is an early sign of pathology in the triple transgenic mouse model of Alzheimer’s disease'. Together they form a unique fingerprint.

Cite this