Exercise as a Therapy for Cognitive Aging and Alzheimer's Disease (2017-2018)

Background

Physical activity and exercise have emerged as important factors associated with lower risks of cognitive decline in normal aging and neurodegenerative disease. Recent advances are identifying the molecular mechanisms that mediate these beneficial effects, providing clinical evidence for the efficacy of exercise in preserving brain function in humans and devising novel therapeutic strategies that include exercise for treating neurological conditions.

However, despite evidence for sex differences in the effects of exercise on cognition and brain physiology, animal studies to unravel the molecular and cellular mechanisms through which exercise alters brain function have focused almost entirely on males.

Almost two-thirds of Americans with Alzheimer’s disease are women, and studies have shown that women have a higher risk for both age-related cognitive decline and Alzheimer’s than do men. Therefore, analysis of the key factors involved in Alzeheimer’s disease in females will fill an important gap in our understanding of the onset and progression of this neurodegenerative disease.

Project Description

This Bass Connections project is designed to understand the basic physiological mechanisms underlying how exercise may be differentially beneficial to males and females. The project team will investigate the potential neuroprotective and cognitive benefits of exercise, particularly aerobic exercise, on the female brain, with a specific focus on the greater susceptibility of females to age-related cognitive decline and neurodegenerative disease.

Team members will use a genetic mouse model of Alzheimer’s disease and wild-type control mice to investigate the mechanisms that mediate the effects of exercise on the brain and periphery (e.g., skeletal muscle, heart), focusing on the mechanisms through which exercise is neuroprotective against aging, neurodegeneration and neurological injury.

The team will develop a model of human female aging in a mouse model of Alzheimer’s disease that includes the process of menopause. Mice and rats do not normally go through a period of irregular cyclicity followed by cessation of ovarian function mid-life. Therefore, we will use a well-developed regimen of treatment with an ovotoxin to produce a menopause-like state in mid-life female mice. This new model will allow us to investigate whether exercise at specific stages of a female’s life—before, during or after menopause—is more or less effective in protecting against the brain pathology and cognitive loss associated with normal aging and with Alzheimer’s disease.

Along with their lab-based research efforts, team members will be involved in the planning and execution of an interdisciplinary symposium, Exercise and the Brain, to be held in 2017-2018, and a related interest group, including inviting speakers, developing the program, advertising and media outreach. Participants will also prepare a one-hour talk for a general audience to translate their scientific knowledge about exercise into therapeutic strategies that women and men could use to improve their brain health or to protect the brain from the ravages of aging and disease.

Anticipated Outcomes

Report including background, methods, results and discussion of the research, intended as a component of an eventual publication in a peer-reviewed journal; research and development of a public presentation providing the science behind exercise’s therapeutic benefits with a focus on women’s health; conference and formation of an interest group

Related Courses

Student team members will be expected to take at least one of the Fall 2017 courses below: 

CULANTH/NEUROSCI/SXL/WOMENST 278/PSY 226 – Sex/Gender-Nature/Nurture (Instructors: Christina Williams and Ara Wilson)

PHYSEDU 207/PSY 214 – Exercise and Mental Health (Instructor: Kim N. McNally)

Student Opportunities

Students will get training and develop expertise in examining cognitive function in mice (behavioral analysis), neurodegeneration and neurogenesis (neuroanatomy), neuronal signaling and synaptic function, mitochondrial function and metabolism as well as brain and muscle energetics.

Students will be engaged in cutting-edge neuroscience research that is developing a more human-like animal model of female brain aging. They will be involved in the planning and promotion of a Duke symposium and interest group on exercise and brain function, and will use their knowledge gained from these activities to prepare and present a talk to the general public showing how science research on exercise can be used to better plan exercise regimens for women and men.

Students will learn about the biology of sex differences, the mechanisms through which exercise alters body, brain and behavior, and gain experience doing state-of-the-art, hands-on research in the field of integrative neuroscience. In order to do this research, they will learn about the ethics of working with rodents and the value of animal research to study human disease, by taking online training in the handling and care of rodents in research. They will also learn how to translate basic science into possible therapeutic interventions and present their understanding and suggestions to a general audience so that that the science is accessible and usable for the listeners.

The team will include 3-4 undergraduates, ideally those who have already taken some biology, chemistry and/or neuroscience (Biological Bases of Behavior and/or Fundamentals of Neuroscience) and are eager to do research that involves animal subjects, along with trainees, graduate students, residents and/or postdocs who are interested and available.

Following the project, team leaders would encourage interested students to continue to do senior thesis research in their laboratories.

Timing

Fall 2017 – Summer 2018

  • Fall 2017: Complete one of two courses: Exercise and Mental Health or Sex/Gender: Nature/Nurture; complete all online training for doing animal research; meet biweekly to plan conference and interest group; option of doing a practicum project in Psychology or Neuroscience to gain laboratory experience relevant to the project
  • Spring 2018: Engage in collaborative neuroscience research in the labs of the project leaders, spending 12-14 hours per week in this independent study doing hands-on laboratory research, background reading, writing; continue to plan and participate in the conference and interest group, meeting with speakers and disseminating information to the media
  • Summer 2018: Continue laboratory research (40+ hours per week for 8 weeks), stipend supported; plan public presentation for September 2018

Crediting

Practicum credit (one-half credit) available for Fall 2017; independent study credit (1 full credit) available for Spring 2018; summer funding

Faculty/Staff Team Members

Carol Colton, School of Medicine - Neurology
Elizabeth Finch, School of Medicine - Department of Medicine*
Kimberly McNally, Duke Recreational & Physical Education
Christina L. Williams, Trinity - Psychology & Neuroscience*
Ara Wilson, Trinity - Gender, Sexuality & Feminist Studies

Graduate Team Members

Sara Maurer, Graduate School - Psychology and Neuroscience

* denotes team leader

Status

Active