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Age and Alzheimer’s Disease Pathology Related Impairment of the Regional Cerebral Blood Flow Response to Mitochondrial KATP Channel Activation in Mouse Models

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • Dong Liu
  • JongH Lee
  • Mark Mattson


The cognitive capacity of the brain is critically dependent upon neurovascular function and dynamic cerebral blood flow (rCBF). The KATP channel is an energy state-dependent K+ channel that is involved in the regulation of neurovascular tone and dynamic rCBF. We measured rCBF responses to KATP channel activator diazoxide in middle-age and old wild type (WT) mice and 3xTgAD mice. Diazoxide was administrated intravenously, and rCBF was monitored with a fiber optic probe. Diazoxide induced a 20-60% increase of rCBF in 12 month-old WT mice, whereas in age-matched 3xTgAD mice the rCBF response to diazoxide was reduced. Immunohistology revealed a moderate accumulation of amyloid beta deposits in brain parenchyma of the 12M 3xTgAD mice. The rCBF response was reduced in 24M WT mice compared to 12M WT mice. In 24M 3xTgAD mice, which exhibit extensive amyloid beta-peptide deposits, the rCBF response was negligible or absent. A mitochondrial KATP channel blocker reduced basal rCBF level and rCBF response to diazoxide in WT mice. Our findings demonstrate an age- and AD- related decline of neurovascular function. Therapeutic interventions that activate KATP channels improve cerebrovascular function and may improve cognitive function in aging and AD.

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