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Role of microRNA-126 in vascular cognitive impairment in mice

Peng Yu1,2,3, Poornima Venkat2, Michael Chopp2,4

  • 1Department of Neurosurgery, Tianjin Medical University General Hospital, China.

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
|September 15, 2018
PubMed

Insights

Vascular dementia (VaD) causes cognitive decline and white matter damage. Reduced microRNA-126 (miR-126) in blood vessels worsens these effects, suggesting miR-126 is crucial for brain health in VaD.

Area of Science:

  • Neuroscience
  • Vascular Biology
  • Molecular Biology

Background:

  • Vascular dementia (VaD) is a common cause of cognitive and memory impairment.
  • MicroRNA-126 (miR-126) plays a key role in regulating vascular function and angiogenesis.
  • Understanding the molecular mechanisms underlying VaD is critical for developing effective treatments.

Purpose of the Study:

  • To investigate the role of miR-126 in cognitive dysfunction, white matter damage, and glymphatic dysfunction in a mouse model of VaD.
  • To determine if reduced miR-126 expression in endothelial cells contributes to VaD pathogenesis.

Main Methods:

  • A multiple microinfarction (MMI) model was used to induce VaD in wild-type (WT) mice.
  • Cerebral blood flow (CBF), vessel patency, glymphatic function, and cognitive function were assessed.
  • Conditional knockout mice lacking miR-126 in endothelial cells (miR-126EC-/-) were used to evaluate the specific role of endothelial miR-126.

Main Results:

  • MMI induced significant cognitive deficits, reduced CBF and vessel patency, white matter damage, and impaired glymphatic function in WT mice.
  • Serum miR-126 levels were decreased following MMI.
  • miR-126EC-/- mice exhibited exacerbated cognitive impairment, reduced CBF, myelin and axon density, and impaired glymphatic function compared to controls.

Conclusions:

  • Endothelial miR-126 plays a protective role in the brain following MMI-induced VaD.
  • Reduced miR-126 expression in endothelial cells may mediate cognitive impairment and white matter damage in VaD.
  • Targeting miR-126 could be a potential therapeutic strategy for VaD.
Keywords:
Aquaporin 4cognition disordersmicroRNA-126vascular dementiawhite matter

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