Poster Title

Elevated Pax3+ cell number potentially compensates for Pax7+ cell-depletion in diaphragm muscle of running mice.

Grade Level at Time of Presentation

Senior

Institution

University of Kentucky

KY House District #

6

KY Senate District #

6

Department

Dept. of Rehabilitation Sciences and the College of Health Sciences

Abstract

Elevated Pax3+ cell number potentially compensates for Pax7+ cell depletion in diaphragm muscle of running mice.

Lina S. Ghazala1; Amy L. Confides2; Kevin Murach, PhD2; Janna Jackson, PhD2; Linda McLoon, PhD3, Esther E. Dupont-Versteegden, PhD2

Departments of 1Biology, 2Rehabilitation Sciences and the College of Health Sciences, University of Kentucky, Lexington, KY, 3Departments of Ophthalmology and Visual Neurosciences, and Neuroscience, University of Minnesota, Minneapolis, MN

Satellite cell-depletion in hind limb muscles does not affect hypertrophy, sarcopenia or the ability to adapt to aerobic exercise. However, the ability of the constantly active diaphragm muscle to adapt to a stressor such as exercise is decreased with a loss of satellite cells is unknown. We hypothesized that satellite cell-depletion would negatively affect diaphragm muscle, particularly with running and in aged mice. We used the Pax7-DTA mouse model to deplete over 90% of Pax7 positive cells in the diaphragm muscle upon treatment with tamoxifen which induces CreER-mediated expression of DTA. Female mice were treated with vehicle or tamoxifen at 4 months of age and were either given running wheels at 6(young) or 22(aged) months of age or remained sedentary for 8 weeks after which they were euthanized. Satellite cell-depletion was associated with 25-28% decreased running activity in young and aged mice. Satellite cell-depletion had no effect on fiber type distribution or cross sectional area of fibers in both young and aged mice regardless of running activity. Minimal effect was observed on diaphragm function measured using on ultrasound analysis. There was no significant difference in myonuclear abundance among treatment and activity groups suggesting that there may be another stem cell type present in the diaphragm muscle of satellite cell-depleted mice which could compensate for the loss of Pax7+ cells. We used fluorescent in situ hybridization to detect Pax3+ cells and found an increased abundance of these cells in young and aged diaphragm muscle in satellite cell-depleted mice. We were unable to detect Pitx2+ cells in both young and aged diaphragm muscle. These results indicate that satellite cell-depletion does not negatively affect diaphragm muscle independent of running activity and conclude that the increased presence of Pax3+ cells in satellite cell-depleted diaphragm muscle potentially compensates for the loss of Pax7+ cells. Supported by NIA AG043721.

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Elevated Pax3+ cell number potentially compensates for Pax7+ cell-depletion in diaphragm muscle of running mice.

Elevated Pax3+ cell number potentially compensates for Pax7+ cell depletion in diaphragm muscle of running mice.

Lina S. Ghazala1; Amy L. Confides2; Kevin Murach, PhD2; Janna Jackson, PhD2; Linda McLoon, PhD3, Esther E. Dupont-Versteegden, PhD2

Departments of 1Biology, 2Rehabilitation Sciences and the College of Health Sciences, University of Kentucky, Lexington, KY, 3Departments of Ophthalmology and Visual Neurosciences, and Neuroscience, University of Minnesota, Minneapolis, MN

Satellite cell-depletion in hind limb muscles does not affect hypertrophy, sarcopenia or the ability to adapt to aerobic exercise. However, the ability of the constantly active diaphragm muscle to adapt to a stressor such as exercise is decreased with a loss of satellite cells is unknown. We hypothesized that satellite cell-depletion would negatively affect diaphragm muscle, particularly with running and in aged mice. We used the Pax7-DTA mouse model to deplete over 90% of Pax7 positive cells in the diaphragm muscle upon treatment with tamoxifen which induces CreER-mediated expression of DTA. Female mice were treated with vehicle or tamoxifen at 4 months of age and were either given running wheels at 6(young) or 22(aged) months of age or remained sedentary for 8 weeks after which they were euthanized. Satellite cell-depletion was associated with 25-28% decreased running activity in young and aged mice. Satellite cell-depletion had no effect on fiber type distribution or cross sectional area of fibers in both young and aged mice regardless of running activity. Minimal effect was observed on diaphragm function measured using on ultrasound analysis. There was no significant difference in myonuclear abundance among treatment and activity groups suggesting that there may be another stem cell type present in the diaphragm muscle of satellite cell-depleted mice which could compensate for the loss of Pax7+ cells. We used fluorescent in situ hybridization to detect Pax3+ cells and found an increased abundance of these cells in young and aged diaphragm muscle in satellite cell-depleted mice. We were unable to detect Pitx2+ cells in both young and aged diaphragm muscle. These results indicate that satellite cell-depletion does not negatively affect diaphragm muscle independent of running activity and conclude that the increased presence of Pax3+ cells in satellite cell-depleted diaphragm muscle potentially compensates for the loss of Pax7+ cells. Supported by NIA AG043721.