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Biology subjects

van de Vijver, D.

Publications and source records attributed to van de Vijver, D..

3 recordsLinked to original sources

Investigating the effects of prednisolone on behavior in mouse models of Duchenne muscular dystrophy

BackgroundNext to progressive muscle loss, Duchenne muscular dystrophy patients suffer from behavioral and cognitive problems. This is due to mutations in the DMD gene, that result in the lack of dystrophin in both the muscles and brain. As part of the standards of care, patients receive corticosteroids (prednisolone or deflazacort) to slow down muscle degeneration. The precise consequences of chronic corticosteroid usage on the behavior of DMD patients remain unclear, mainly due to challenges of recruiting corticosteroid naive patients into clinical studies. ObjectiveThis study used DMD mouse models, representing mutations resulting in lack of one or more dystrophin isoforms, to analyze the effects of corticosteroid treatment on different behavioral domains. MethodsPrednisolone (PDN) or placebo was administered via a subcutaneous 60-day slow release pellet (66 {micro}g/day) and mice were subjected to several behavioral tests. ResultsUnfortunately, the pellet only exposed mice to PDN for half of the intended duration. During the time of PDN exposure, we found a small amelioration in anxiety but were unable to find any differences in social interaction and spatial learning and memory. ConclusionsShort term exposure to PDN via a slow release pellet does not seem to negatively affect anxiety, social interaction or spatial learning and memory. We cannot rule out that a longer treatment period than 4 weeks would affect behavior in DMD mice.

animal behavior and cognition↗

The vitamin B3 analogue nicotinamide riboside has only very minor effects on reducing muscle damage in mdx mice

BACKGROUNDVitamin B3 analogue nicotinamide riboside (NR) has been suggested to have beneficial effects on muscle pathology in a mouse model for Duchenne muscular dystrophy (DMD). In muscle dystrophy, NR is thought to act acts by increasing levels of NAD+, to improve mitochondrial functioning and reduce muscle pathology. OBJECTIVEWe here aimed to validate the effects of NR to improve muscle quality after eight weeks of treatment in two different mouse models for DMD: the commonly used mdx mouse on a C57BL/10 background (BL10mdx) and the more severely affected mdx mouse on a DBA/2J background (D2-mdx). METHODSTo study in more detail whether NR treatment had an impact on muscle pathology, we assessed the expression levels of several markers for DMD pathology (fibrosis, regeneration and inflammation) in diaphragm. RESULTSOur data showed a trend for increase in NAD+-levels in blood; only in the D2-mdx NR-treated mice the NAD+-levels were slightly increased. These markers were elevated in mdx models compared to controls, but not affected by the NR treatment. Histological analysis of muscle tissues indicated a mild treatment effect in D2-mdx mice. CONCLUSIONSBased on our results, testing NR treatment in clinical trials in DMD patients is not warranted.

genetics↗

High-throughput data-driven analysis of myofiber composition reveals muscle-specific disease and age-associated patterns

Contractile properties of myofibers are dictated by the abundance of myosin heavy chain (MyHC) isoforms. MyHC composition designates muscle function and its alterations could unravel differential muscle involvement in muscular dystrophies and aging. Current analyses are limited to visual assessments in which myofibers expressing multiple MyHC isoforms are prone to misclassifications. As a result, complex patterns and subtle alterations are unidentified. We developed a high-throughput data-driven myofiber analysis to quantitatively describe the variations in myofibers across the muscle. We investigated alterations in myofiber composition between genotypes, two muscles and two age groups. We show that this analysis facilitates the discovery of complex myofiber compositions and its dependency on age, muscle type and genetic conditions.\n\nNonstandard abbreviations

bioinformatics↗