open access publication

Article, 2024

Mouse brain elastography changes with sleep/wake cycles, aging, and Alzheimer's disease

NeuroImage, ISSN 1095-9572, 1053-8119, Volume 295, Page 120662, 10.1016/j.neuroimage.2024.120662

Contributors

Ge, Gary Ruian [1] Song, Wei [2] Giannetto, Michael J 0000-0002-4338-8709 [2] Rolland, Jannick P 0000-0003-2747-4022 [1] Nedergaard, Maiken (Corresponding author) [2] [3] Parker, Kevin J 0000-0002-6313-6605 (Corresponding author) [1] [2]

Affiliations

  1. [1] University of Rochester
    2. [NORA names: United States; America, North; OECD];
  2. [2] University of Rochester Medical Center
    3. [NORA names: United States; America, North; OECD];
  3. [3] University of Copenhagen
    4. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD]

Abstract

Understanding the physiological processes in aging and how neurodegenerative disorders affect cognitive function is a high priority for advancing human health. One specific area of recently enabled research is the in vivo biomechanical state of the brain. This study utilized reverberant optical coherence elastography, a high-resolution elasticity imaging method, to investigate stiffness changes during the sleep/wake cycle, aging, and Alzheimer's disease in murine models. Four-dimensional scans of 44 wildtype mice, 13 mice with deletion of aquaporin-4 water channel, and 12 mice with Alzheimer-related pathology (APP/PS1) demonstrated that (1) cortical tissue became softer (on the order of a 10% decrease in shear wave speed) when young wildtype mice transitioned from wake to anesthetized, yet this effect was lost in aging and with mice overexpressing amyloid-β or lacking the water channel AQP4. (2) Cortical stiffness increased with age in all mice lines, but wildtype mice exhibited the most prominent changes as a function of aging. The study provides novel insight into the brain's biomechanics, the constraints of fluid flow, and how the state of brain activity affects basic properties of cortical tissues.

Keywords

APP/PS1, AQP4, Alzheimer, Alzheimer's disease, Alzheimer-related pathology, activity, age, amyloid-b, aquaporin-4 water channels, area, biomechanical state, biomechanics, brain, brain activity, brain biomechanics, changes, channel, cognitive function, constraints, cortical stiffness, cortical tissue, cycle, deletion, disease, disorders, effect, elasticity imaging methods, elastography, flow, fluid flow, four-dimensional scan, function, function of age, health, human health, imaging methods, lines, method, mice, model, mouse lines, murine model, neurodegenerative disorders, optical coherence elastography, pathology, physiological processes, priority, process, properties, research, scanning, sleep/wake, sleep/wake cycle, state, states of brain activity, stiffness, stiffness changes, study, tissue, water, water channel AQP4, water channels, wildtype mice, young wildtype mice

Funders

  • National Center for Complementary and Integrative Health
  • United States Department of the Army
  • Lundbeck Foundation
  • International Human Frontier Science Program Organization
  • Simons Foundation
  • Adelson Foundation
  • National Institute of Neurological Disorders and Stroke
  • Novo Nordisk (Denmark)
  • National Institute on Aging
  • United States Army Research Office

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