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Christiane Wrann, DVM, PhD

Pronouns

She/Her/Hers

Rank

Assistant Professor

Institution

MGH

BWH-MGH Title

Assistant Investigator

Department

Medicine

Authors

Mohammad R. Islam1,11, Sophia Valaris1,11, Michael F. Young1, Erin B. Haley1, Renhao Luo1, Sabrina F. Bond1,2, Sofia Mazuera1,2, Robert R. Kitchen1, Barbara J. Caldarone3, Luis E.B. Bettio4, Brian R. Christie4, Angela B. Schmider5, Roy J. Soberman5, Antoine Besnard6, Mark P. Jedrychowski7, Hyeonwoo Kim7, Hua Tu8, Eunhee Kim9,10, Se Hoon Choi9,10, Rudolph E. Tanzi9,10, Bruce M. Spiegelman7, Christiane D. Wrann1,10,12,*

Exercise hormone irisin is a critical regulator of cognitive function

I have a strong commitment and proven track record for promoting women and underrepresented groups in science and medicine at MGH. This is reflected in the above-average number of female and URM trainees in my laboratory who have successfully transitioned into the next career step of their first choice.

Our recent study in Nature Metabolism identified the novel exercise hormone irisin as a potential treatment for Alzheimer’s disease. The study was covered by the New York Times, National Geographics, and highlighted by NIH Director Dr. Francis Collins. Based on the IP, I am a cofounder and consultant for Aevum.

Background

Identifying secreted mediators driving the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in aging or Alzheimer’s disease (AD).

Methods & Results

Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the exercise benefits on cognitive function. Genetic deletion of FNDC5/irisin (global F5KO mice) impairs cognitive function in exercise, aging, and AD. Diminished pattern separation in F5KOs can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KO mice, adult-born neurons in the dentate gyrus are morphologically, transcriptionally, and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral delivery of irisin via adeno-associated viral overexpression in the liver, results in enrichment of central irisin and is sufficient to improve both the cognitive deficit and neuropathology in AD mouse models.

Conclusion

Irisin is a crucial regulator of cognitive benefits of exercise and potential therapeutic for treating cognitive disorders including AD.

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