Biology subjects

Wiggs, M. P.

Publications and source records attributed to Wiggs, M. P..

3 recordsLinked to original sources

bioRxiv2025

Pediatric CHOP Chemotherapy Acutely Disrupts Satellite-Cell Dynamics and Blunts Muscle Mass in a Sex-Specific Manner

Pediatric cancer survival now exceeds 85 percent owing, in part, advances and use of combination chemotherapy treatments such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Despite its efficacy, CHOP may cause deleterious off-target effects during critical pediatric development periods such as impairments of skeletal muscle. We evaluated the acute effects of a CHOP administered to C57Bl/6J mice from postnatal day 28 to 48. CHOP slowed body-weight gain and has smaller gastrocnemius fiber cross-sectional area by approximately 25 percent in both sexes. mRNA sequencing detected 214 differentially expressed genes in males and 217 in females relative to controls, yet only 29 transcripts overlapped. Males exhibited downregulation of myogenic regulators, indicating impaired progenitor maintenance, whereas females showed an upregulation of extracellular-matrix and translational machinery genes plus cell-cycle regulators. Using immunohistochemistry to assess satellite cell abundance, there were 60% fewer satellite cells in males and a 40% fewer in females, which supported our transcriptional findings. These results demonstrate that pediatric CHOP acutely disrupts muscle stem-cell dynamics via sex-specific molecular programs and identify satellite-cell depletion as a potential target for preserving muscle health in pediatric cancer survivors.

physiology↗

bioRxiv2025

Differential regulation of mitochondrial quality control in skeletal muscle by HZE radiation exposure and partial weightbearing in mice

Spaceflight places astronauts under both reduced mechanical loading and ionizing radiation, each of which can compromise skeletal muscle health. We investigated whether 21 days of simulated lunar gravity (one sixth G) with or without a single 0.5 Gy dose of 28Si heavy ion radiation alters transcriptional regulators of mitochondrial quality control in mouse gastrocnemius muscle. Female BALB/cByJ mice were assigned to four groups: Sham + 1 G (SHAM+CC), Rad + 1 G (RAD+CC), Sham + G/6 (SHAM+G/6), Rad + G/6 (RAD+G/6) and relative mRNA levels of key regulators of mitochondrial biogenesis, mitophagy, dynamics and electron transport chain content were measured by quantitative RT-PCR. Radiation significantly suppressed PGC-1 (p = 0.035) and TFAM (p = 0.051) transcripts and reduced LC3b (p = 0.033) and Park2 (p = 0.007) expression; no effects of simulated lunar gravity or interaction effects were detected. Composite scores confirmed suppression of biogenesis (p = 0.029) and a trend toward reduced mitophagy (p = 0.057). Transcripts encoding oxidative phosphorylation subunits and fusion and fission factors remained unchanged, suggesting preserved mitochondrial content and network homeostasis at day 21. These findings indicate that a single space relevant heavy ion exposure selectively disrupts early transcriptional steps of mitochondrial turnover without immediately altering organelle abundance of transcripts for electron transport chain or dynamics; in contrast simulated lunar gravity alone did not elicit changes in these pathways.

molecular biology↗

bioRxiv2021

Muscle weakness precedes atrophy during cancer cachexia and is associated with muscle-specific mitochondrial stress

Muscle weakness and wasting are defining features of cancer-induced cachexia. Mitochondrial stress occurs before atrophy in certain muscles, but distinct responses between muscles and across time remains unclear. We aimed to determine the time-dependent and muscle-specific responses to Colon-26 (C26) cancer-induced cachexia in mice. At 2 weeks post-inoculation, the presence of small tumours did not alter body or muscle mass but decreased force production in the quadriceps and diaphragm. Pyruvate-supported mitochondrial respiration was lower in quadriceps while mitochondrial H2O2 emission was elevated in diaphragm. At 4 weeks, large tumours corresponded to lower body mass, muscle mass, and cross-sectional area of fibers in quadriceps and diaphragm. Force production in quadriceps was unchanged but remained lower in diaphragm vs control. Mitochondrial respiration was increased while H2O2 emission was unchanged in both muscles vs control. Mitochondrial creatine sensitivity was compromised in quadriceps. These findings indicate muscle weakness precedes atrophy in quadriceps and diaphragm but is linked to heterogeneous mitochondrial alterations. Eventual muscle-specific restorations in force and bioenergetics highlight how the effects of cancer on one muscle do not predict the response in another muscle. Exploring heterogeneous responses of muscles to cancer may reveal new mechanisms underlying distinct sensitivities, or resistance, to cancer cachexia.

physiology↗