Differentially severe cognitive effects of compromised cerebral blood flow in aged mice: Association with myelin degradation and microglia activation

Gilly Wolf, Amit Lotan, Tzuri Lifschytz, Hagar Ben-Ari, Tirzah Kreisel Merzel, Pavel Tatarskyy, Michael Valitzky, Ben Mernick, Elad Avidan, Nickolay Koroukhov, Bernard Lerer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Bilateral common carotid artery stenosis (BCAS) models the effects of compromised cerebral blood flow on brain structure and function in mice. We compared the effects of BCAS in aged (21 month) and young adult (3 month) female mice, anticipating a differentially more severe effect in the older mice. Four weeks after surgery there was a significant age by time by treatment interaction on the radial-arm water maze (RAWM; p = 0.014): on the first day of the test, latencies of old mice were longer compared to the latencies of young adult mice, independent of BCAS. However, on the second day of the test, latencies of old BCAS mice were significantly longer than old control mice (p = 0.049), while latencies of old controls were similar to those of the young adult mice, indicating more severe impairment of hippocampal dependent learning and working memory by BCAS in the older mice. Fluorescence staining of myelin basic protein (MBP) showed that old age and BCAS both induced a significant decrease in fluorescence intensity. Evaluation of the number oligodendrocyte precursor cells demonstrated augmented myelin replacement in old BCAS mice (p < 0.05) compared with young adult BCAS and old control mice. While microglia morphology was assessed as normal in young adult control and young adult BCAS mice, microglia of old BCAS mice exhibited striking activation in the area of degraded myelin compared to young adult BCAS (p < 0.01) and old control mice (p < 0.05). These findings show a differentially more severe effect of cerebral hypoperfusion on cognitive function, myelin integrity and inflammatory processes in aged mice. Hypoperfusion may exacerbate degradation initiated by aging, which may induce more severe neuronal and cognitive phenotypes.

Original languageAmerican English
Article number191
JournalFrontiers in Aging Neuroscience
Volume9
Issue numberJUN
DOIs
StatePublished - 16 Jun 2017

Bibliographical note

Publisher Copyright:
© 2017 Wolf, Lotan, Lifschytz, Ben-Ari, Kreisel Merzel, Tatarskyy, Valitzky, Mernick, Avidan, Koroukhov and Lerer.

Keywords

  • Aging
  • Bilateral carotid artery stenosis
  • Cerebral hypoperfusion
  • Microglia
  • Mouse model
  • Vascular dementia
  • White matter lesions

Fingerprint

Dive into the research topics of 'Differentially severe cognitive effects of compromised cerebral blood flow in aged mice: Association with myelin degradation and microglia activation'. Together they form a unique fingerprint.

Cite this