Targeting PTEN but not SOCS3 resists an age-dependent decline in promoting axon sprouting

Cédric G. Geoffroy; Jessica M. Meves; Hugo Jae Mun Kim; Daniel Romaus-Sanjurjo; Theresa C. Sutherland; Jeffrey J. Li; Juliet Suen; Joshua J. Sanchez; Binhai Zheng

iScience (Nov 2022)

Targeting PTEN but not SOCS3 resists an age-dependent decline in promoting axon sprouting

Cédric G. Geoffroy,
Jessica M. Meves,
Hugo Jae Mun Kim,
Daniel Romaus-Sanjurjo,
Theresa C. Sutherland,
Jeffrey J. Li,
Juliet Suen,
Joshua J. Sanchez,
Binhai Zheng

Affiliations

Cédric G. Geoffroy: Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University, Bryan, TX, USA; Corresponding author
Jessica M. Meves: Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA; Neurosciences Graduate Program, University of California San Diego, La Jolla, CA, USA
Hugo Jae Mun Kim: Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA
Daniel Romaus-Sanjurjo: Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA
Theresa C. Sutherland: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University, Bryan, TX, USA
Jeffrey J. Li: Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA
Juliet Suen: Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA
Joshua J. Sanchez: Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA
Binhai Zheng: Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA; VA San Diego Research Service, San Diego, CA, USA; Corresponding author

Journal volume & issue: Vol. 25, no. 11
p. 105383

Abstract

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Summary: Axonal repair is critical for functional recovery after injury of the CNS. We previously reported that neuronal PTEN deletion exhibits an age-dependent decline in promoting axon regeneration from the corticospinal tract (CST). How sprouting of uninjured axons, a naturally occurring form of axonal repair, is impacted by age is unknown. We assessed CST sprouting after unilateral pyramidotomy in PTEN and/or SOCS3-deleted mice at different ages. While PTEN deletion enhances sprouting independently of age, SOCS3 deletion loses its sprouting-promoting effect with age. The synergistic effect of PTEN/SOCS3 co-deletion on CST sprouting is rapidly lost with increased age. Overall, promoting sprouting appears more robust across age than regeneration, yet distinct molecular pathways are differentially impacted by age. Importantly, six-week delayed PTEN deletion promotes CST sprouting across age groups, supporting a clinically relevant time frame for this neural repair strategy independently of age.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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