bioRxiv Science⌕ Search

Biology subjects

Reitzner, S. M.

Publications and source records attributed to Reitzner, S. M..

7 recordsLinked to original sources

Reduced physiological reserve and a blunted response to acute exercise in adults with cerebral palsy

Cerebral palsy (CP) is an early-onset neurodevelopmental condition associated with metabolic impairment and an increased risk of non-communicable diseases across the lifespan. However, the basis of these changes remains largely unknown. This study provides a comprehensive cardiometabolic and physical function profile of 23 adults with CP relative to 33 typically developing (TD) adolescents and 61 TD adults. Compared to TD individuals, adults with CP exhibited reduced cardiorespiratory fitness, smaller cardiac dimensions, and lower muscle mass. Circulating metabolomic and proteomic profiling identified a distinct molecular signature in CP, including altered tricarboxylic acid (TCA) cycle metabolites, and elevated myostatin, matrix-related proteins and pro-inflammatory cytokines. We further tested the capacity for physiological and molecular adaptation using an acute bout of endurance exercise. In response to exercise, individuals with CP exhibited an attenuated response compared to TD groups, characterized by a blunted lactate response and lower venous oxygen levels. TD participants also increased canonical exercise-responsive factors, including NADK, IL-8, ANGPTL1 and GDF15, whereas these responses were attenuated in CP. These novel findings define a distinct cardiometabolic profile in adults with CP at rest and reveal an attenuated molecular response to exercise. These data carry implications for targeted interventions and prevention strategies across the lifespan.

physiology↗

Transcriptomic Profiling of scWAT Reveals Reduced Lipid-Associated Macrophage Signatures in Long-Term Endurance- and Resistance-Trained Athletes

Regular exercise training is associated with systemic and tissue-specific performance and health benefits, yet long-term molecular adaptations in subcutaneous abdominal white adipose tissue (scWAT) remain unclear. We analyzed the resting scWAT transcriptome of 89 adults (35-50 years) who were long-term (>15 years) endurance- or strength-trained, or untrained. Long-term training was linked to enrichment of ribosomal, mitochondrial, and aerobic metabolism-related pathways, while immune-related pathways were enriched in untrained individuals. A distinct sex dimorphic scWAT was identified: untrained females exhibited a more metabolically favorable, trained-like transcriptomic profile, and untrained males an untrained-like profile. In trained males, the inflammatory gene signature was lower than in untrained males. We also identified 11 genes specific to lipid-associated macrophages with lower expression in trained individuals, particularly in all endurance-trained individuals and strength-trained females. These findings highlight sex-specific, exercise-induced adaptations in scWAT relevant to metabolic health, and underscore the importance of including both sexes in scWAT research.

physiology↗

Endurance Exercise Elevates Plasma Mature Brain-Derived Neurotrophic Factor through Child- and Adulthood, with Amplified Effects in Adults

BackgroundBrain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a central role in neuronal health. BDNF exists in two primary isoforms, the mature form (mBDNF) and its precursor (proBDNF), with opposing downstream effects on neuronal function. The positive effect of exercise on plasma levels of the BDNF-isoforms has been extensively studied in adults. However, equivalent investigations are lacking in children and youth. MethodsTwenty healthy children (9-12 years old), 19 adolescents (13-17 years old), and 39 adults (23-49 years old) donated venous blood before and after a 45-minute run. Platelet-poor plasma was analyzed for pro- and mBDNF using enzyme-linked immunosorbent assay. Maximal oxygen uptake and anthropometric data were assessed in all participants, while Tanner stage, circulating sex hormones, and accelerometry-based activity level were assessed in children and adolescents. ResultsWe found that children, adolescents, and adults have similar basal levels of pro-(337-543 pg x ml-1) and mBDNF (650-1111 pg x ml-1). For children and adolescents, basal levels of mBDNF correlated with average time spent in vigorous activity (r=0.5794, p=0.0015). In response to acute endurance exercise, mBDNF increased by 701 {+/-} 946, 1232 {+/-} 1105, and 1557 {+/-} 1168 pg x ml-1 in children, adolescents, and adults, respectively. The acute endurance exercise did not affect proBDNF levels (p>0.05). ConclusionOur results demonstrate that basal plasma pro- and mBDNF levels do not depend on age and maturity. Plasma mBDNF levels increase following endurance exercise in all age groups, but to a greater extent in adults. Highlights/ImpactO_LIWe show that in children and adolescents, regular vigorous physical activity is key to increased basal levels of plasma mBDNF, a factor linked to neuroplasticity and brain health. C_LIO_LIThe ability to elevate mBDNF through exercise is present across all age groups, with the greatest increase in adults. C_LIO_LIThe mBDNF response to physical exercise seems to be independent of underlying physical fitness. C_LIO_LIOur findings suggest that basal plasma mBDNF levels may reflect the cumulative effects of repeated exercise rather than an individuals overall physical fitness. C_LI

physiology↗

Scalable in-vitro immunostimulation of human blood for in-depth profiling of acute immune response effects

In-vitro immune stimulation of whole blood has great analytic potential for exploring the immune system function. However, logistical and biological constraints might limit the extent to which such investigations can be performed. Flexible and often even low-tech mobile applicability can increase the diversity of conditions that can be investigated. To this end, we developed and optimized a medium that enables prolonged in-vitro stimulation and enables highly functional immune responses within 24 hours of incubation. In addition, we also developed and optimized a low-tech water-based mobile incubator to enable logistical flexibility. Finally, we describe the implementation of both systems using a practical example of sample collection at a sampling site with no access to laboratory equipment outside of a research lab.

immunology↗

Molecular profiling of high-level athlete skeletal muscle after acute exercise - a systems biology approach

Life-long high-level exercise training leads to improvements in physical performance and multi-tissue adaptation following changes in molecular pathways. While skeletal muscle baseline differences between exercise-trained and untrained individuals have been previously investigated, it remains unclear how acute exercise multi-omics are influenced by training history. We recruited and extensively characterized 24 individuals categorized as endurance athletes, strength athletes or control subjects. Multi-omics profiling was performed from skeletal muscle before and at three time-points after endurance or resistance exercise sessions. Timeseries multi-omics analysis revealed distinct differences in molecular processes such as fatty- and amino acid metabolism and for transcription factors such as HIF1A and the MYF-family between both exercise history and acute form of exercise. Furthermore, we found a "transcriptional specialization effect" by transcriptional narrowing and intensification. Finally, we performed multi-omics network analysis and clustering, providing a novel resource of skeletal muscle transcriptomic and metabolomic profiling in highly trained and untrained individuals.

physiology↗

Circulating immune cell populations at rest and in response to acute endurance exercise in young adults with cerebral palsy

AimLow physical activity alters immune function and increases the risk of developing chronic inflammation. This cross-sectional study aimed at determining the immune status and function in young adults with cerebral palsy (CP) in comparison to typically developing (TD) individuals. MethodBlood samples from 12 individuals with CP and 17 TD were collected before, immediately after, and one hour following 45 minutes of Frame Running or running, respectively. Independent t-tests were used to compare heart rate, level of exertion, and baseline cell proportions between groups. Mixed model ANOVA was utilized to investigate immune cell responses to exercise across groups. ResultsBaseline levels of TCR{gamma}{delta}+ T-cells were significantly higher in the individuals with CP. Several cell populations showed significant changes after exercise in both CP and TD groups. CD8+ T-cells were only significantly elevated immediately after exercise in the TD participants. Individuals with CP exhibited significantly lower heart rates, despite similar ratings of perceived exertion. InterpretationElevated baseline TCR{gamma}{delta}+ T-cells may indicate low-grade inflammation in adults with CP. Although most of the cell populations showed typical responses to endurance exercise, the absence of response in CD8+ T-cells in individuals with CP may indicate the need for higher intensity during exercise. What this paper addsO_LIThis is the first study addressing immune cells in adults with CP C_LIO_LITCR{gamma}{delta}+ T-cell baseline levels are elevated in adults with CP C_LIO_LIThe CD8+ T-cell response to exercise was blunted in adults with CP C_LIO_LIExercise intensity is decisive for CD8+ T-cell responses in individuals with CP C_LI

immunology↗

FiNuTyper: an automated deep learning-based platform for simultaneous fiber and nucleus type analysis in human skeletal muscle

SummaryWhile manual quantification is still considered the gold standard for skeletal muscle histological analysis, it is time-consuming and prone to investigator bias. We assembled an automated image analysis pipeline, FiNuTyper (Fiber and Nucleus Typer), from recently developed deep learning-based image segmentation methods, optimized for unbiased evaluation of fresh and postmortem human skeletal muscle. We validated and utilized SERCA1 and SERCA2 as type-specific myonucleus and myofiber markers. Parameters including myonuclei per fiber, myonuclear domain, central myonuclei per fiber, and grouped myofiber ratio were determined in a fiber type-specific manner, revealing a large degree of gender- and muscle-related heterogeneity. Our platform was also tested on pathological muscle tissue (ALS) and adapted for the detection of other resident cell types (leukocytes, satellite cells, capillary endothelium). In summary, we present an automated image analysis tool for the simultaneous quantification of myofiber and myonuclear types, to characterize the composition of healthy and diseased human skeletal muscle. HighlightsO_LIA deep learning-based automated platform for skeletal muscle microscopic analysis C_LIO_LIHigh-fidelity identification and characterization of myonuclei and myofibers C_LIO_LIValidation of SERCA1 and SERCA2 as markers for myofiber and myonuclear subtypes C_LIO_LICharacterization of healthy and pathological human skeletal muscle tissue features C_LIO_LIAdaptations provided for studies on other resident cell types like satellite cells C_LI eTOC BlurbAn automated platform for unbiased analysis of skeletal muscle immunohistochemical images, focusing on type-specific myofiber-myonucleus relationships, facilitating high-throughput studies of healthy and diseased tissues.

cell biology↗