Biology subjects

Noort, W.

Publications and source records attributed to Noort, W..

7 recordsLinked to original sources

bioRxiv2026

Effects of lumbar disc injury and nociception on trunk motor control during rat locomotion

Intervertebral disc (IVD) injury is a major cause of low-back pain and can lead to structural deficits and mechanical instability. When the IVD is compromised, neuromuscular compensation by paraspinal muscles, such as the multifidus (MF) and longissimus (ML), is critical for maintaining spine stability. However, it is unknown how IVD injury and its interaction with nociception affect neuromuscular control. This study assessed the effects of IVD injury and additional muscle-derived nociception on trunk motor control during locomotion in a rat model. IVD injury was induced via needle puncture at L4/L5. One week later, hypertonic saline was injected into the lumbar MF to induce nociception. Trunk and pelvic kinematics, bilateral EMG activity of MF and ML were recorded during treadmill locomotion at baseline, one week after IVD injury, and immediately following hypertonic saline injection. Trunk and pelvic kinematics and bilateral muscle activation patterns remained largely consistent across conditions. No significant changes were found in stride duration, pelvic, lumbar and spine angle changes, variability, or movement asymmetry. MF activation was bilaterally synchronized, whereas ML showed left-right alternating activation patterns. Following IVD injury, right MF mean activation and EMG variability increased significantly compared to baseline. When muscle-derived nociception was added in the unstable spine (IVD injury) condition, left MF minimum amplitude was significantly reduced, and instability-related increases in right MF mean activation and variability were attenuated, but not fully reversed. These findings suggest that IVD injury, alone or in combination with muscle-derived nociception, elicits localized neuromuscular adaptations without disrupting the global locomotor patterns.

neuroscience↗

bioRxiv2025

Maximising average mechanical power output during stretch-shortening cycles of rat medial gastrocnemius muscle

The average mechanical power output (AMPO) during a stretch-shortening cycle produced by a muscle depends on muscle length and stimulation over time. While the effects of cycle frequency and muscle length excursion on AMPO are well-known, several questions remain about the effects of muscle length and stimulation over time on the maximal attainable AMPO. For example, which precise muscle length and stimulation over time yield maximal AMPO? In situ experiments are inherently limited to a finite set of muscle length and stimulation over time. To overcome this limitation, we combined in situ experiments on rat m. gastrocnemius medialis with Hill-type muscle modelling. We first performed dedicated trials to estimate the muscle-tendon-complex (MTC) properties of each rat. Subsequently, we performed various stretch-shortening cycles with substantial differences in cycle frequency, shortening-to-lengthening time ratio and MTC length excursion. Model-predicted AMPO correlated nearly perfect with experimentally measured AMPO (r2 > 0.98). This justified further exploration using the Hill-type MTC model. Using the Hill-type MTC model, we predicted that AMPO peaks at a cycle frequency of 3.5 Hz, with a shortening-to-lengthening time ratio of 6:1 and an MTC length excursion of 8 mm. Notably, cycle frequency and MTC length excursion showed a strong interaction: increasing one necessitated a decrease in the other to maximise AMPO. By contrast, the optimal shortening-to-lengthening time ratio remained remarkably constant across all tested combinations of cycle frequency and MTC length excursion. This shows that muscles should spend substantially more time shortening than lengthening to maximise AMPO.

physiology↗

bioRxiv2025

An in vivo rat lumbar spine instability model induced by intervertebral disc injury

Intervertebral disc (IVD) degeneration is a potential contributor to low-back pain. While experimental IVD injury models have demonstrated IVD structural changes, the early mechanical consequences remain unclear. This study aimed to establish a rat model of lumbar spine instability via IVD injury and assess back musculature adaptations to IVD injury. Thirty-one adult male Wistar rats were assigned to three groups: IVD knife stab lesion (knife), IVD needle puncture (needle), and sham surgery control (control). In the knife and needle groups, L4/L5 IVDs were injured at 14 weeks of age. One-two weeks post-intervention, lumbar multifidus (MF) and medial longissimus (ML) muscles were excised, L4-L5 spinal segments were harvested for mechanical testing, and IVDs were collected for histology. The needle group exhibited lower peak stiffness, peak moment, and hysteresis than controls in flexion, with no difference in lateral bending. IVD height and area did not differ between groups, but the needle group had a smaller nucleus relative to annulus area compared to controls. Morphological changes were observed in both injury groups. The needle group showed higher normalized ML mass, while normalized MF mass was unchanged. In conclusion, a rat model of lumbar spine instability was successfully established via IVD needle injury.

bioengineering↗

bioRxiv2023

Skeletal Muscle Phenotype-Specific Effects of ACVR1B and TGFBR1 Receptor Signalling on Muscle Transcriptome, Force generation and Metabolism

Transforming growth factor-{beta} (TGF-{beta}) signaling is associated with progressive skeletal muscle wasting and fibrosis, while double knockout of TGF-{beta} type I receptors Acvr1b and Tgfbr1 results in hypertrophy. Gaining insights in how myofibre-specific knockout of these receptors affects muscle transcriptome, strength and mitochondrial activity could aid in the development of therapeutic interventions to improve muscle function. Here, we show that 3 months of myofibre-specific knockout of both receptors (dKO) in mice induced a 1.6-fold increase in gastrocnemius medialis mass and a 1.3-fold increase in maximal force. Soleus muscle mass and maximal force both increased 1.2-fold in dKO mice. Muscle hypertrophy in dKO mice was accompanied by a proportional increase in succinate dehydrogenase enzyme activity. Single receptor knockout caused minor phenotypical alterations. Transcriptome analyses revealed that gastrocnemius medialis had 1811 and soleus had 295 differentially expressed genes, mainly related to muscle contraction, hypertrophy, filament organization and oxidative metabolism. Hgf and Sln genes were strongly upregulated in both muscles of dKO mice, while Sntb1 was downregulated. This in combination of transcriptional changes are associated with muscle hypertrophy and increased mitochondrial biosynthesis. Our study highlights that myofibre-specific interference with both TGF-{beta} type I receptors concurrently stimulates myofibre hypertrophy and mitochondrial activity.

physiology↗

bioRxiv2023

Oncogene EVI1 Drives Acute Myeloid Leukemia Via a Targetable Interaction with CTBP2

Acute myeloid leukemia (AML) driven by the activation of EVI1 due to chromosome 3q26/MECOM rearrangements is incurable. Since transcription factors like EVI1 are notoriously hard to target, insight into the mechanism by which EVI1 drives myeloid transformation could provide alternative avenues for therapy. Applying protein folding predictions combined with proteomics technologies, we demonstrate that interaction with CTBP1 and CTBP2 via a single PLDLS motif in EVI1 is indispensable for leukemic transformation. Furthermore, we show that a 4x PLDLS repeat construct outcompetes binding of EVI1 to CTBP1 and CTBP2 and thereby inhibits proliferation of 3q26/MECOM rearranged AML both in in vitro and in xenotransplant models. This proof-of-concept study opens the possibility to therapeutically target one of the most incurable forms of AML with specific EVI1-CTBP inhibitors. This has important implications for other tumour types with aberrant expression of EVI1 as well as for cancers transformed by distinct CTBP-dependent oncogenic transcription factors.

cancer biology↗

bioRxiv2020

Glycine receptor subunit-β -deficiency in a mouse model of spasticity results in attenuated physical performance, growth and muscle strength

Spasticity is the most common neurological disorder associated with increased muscle contraction causing impaired movement and gait. The aim of this study was to characterize physical performance and skeletal muscle function and phenotype of mice with a hereditary spastic mutation (B6.Cg-Glrbspa/J). Motor function, gait and physical activity of juvenile and adult spastic mice and the morphological, histological and mechanical characteristics of their soleus (SO) and gastrocnemius medialis (GM) muscles were compared with their wild-type (WT) littermates. Spastic mice showed attenuated growth, impaired motor function and low physical activity. Gait of spastic mice was characterized by a typical hopping pattern. Spastic mice showed lower muscle forces, which were related to the smaller physiological cross-sectional area of spastic muscles. The muscle-tendon complex length-force relationship of adult GM was shifted towards shorter lengths, which was explained by attenuated longitudinal tibia growth. Spastic GM was more fatigue resistant than WT GM. This was largely explained by a higher mitochondrial content in muscle fibers and relatively higher percentage of slow type muscle fibers. Muscles of juvenile spastic mice showed similar differences compared to WT juvenile mice, but these were less pronounced than between adult mice. This study shows that in spastic mice, disturbed motor function and gait is likely the result hyperactivity of skeletal muscle and impaired skeletal muscle growth, which progress with age.

physiology↗

bioRxiv2018

A metabolic switch from OXPHOS to glycolysis is essential for cardiomyocyte proliferation in the regenerating heart

The capacity to regenerate damaged tissues, such as the heart, various enormously amongst species. While heart regeneration is generally very low in mammals 1-3, it can regenerate efficiently in certain amphibian and fish species 4,5. Zebrafish has been used extensively to study heart regeneration, resulting in the identification of proliferating cardiomyocytes that drive this process 5-7. However, mechanisms that drive cardiomyocyte proliferation are largely unknown. Here, using a single-cell mRNA-sequencing approach, we find a transcriptionally distinct population of dedifferentiated and proliferating cardiomyocytes in regenerating zebrafish hearts. While adult cardiomyocytes are known to rely on mitochondrial oxidative phosphorylation (OXPHOS) for energy production, these proliferating cardiomyocytes show reduced mitochondrial gene expression and decreased OXPHOS activity. Strikingly, we find that genes encoding rate-limiting enzymes of the glycolysis pathway are induced in the proliferating cardiomyocytes, and inhibiting glycolysis impairs cardiomyocyte cell cycle reentry. Mechanistically, glycolytic gene expression is induced by Nrg1/Erbb2 signaling, and this is conserved in a mouse model of enhanced regeneration. Moreover, inhibiting glycolysis in murine cardiomyocytes abrogates the mitogenic effects of Nrg1/ErbB2 signaling. Together these results reveal a conserved mechanism in which cardiomyocytes undergo metabolic reprogramming by activating glycolysis, which is essential for cell cycle reentry and heart regeneration. This could ultimately help develop therapeutic interventions that promote the regenerative capacity of the mammalian heart.

cell biology↗