Evidence map›Paper›PMID 39123261›Full record

ArticleSkeletal muscle2024

Pilot investigations into the mechanistic basis for adverse effects of glucocorticoids in dysferlinopathy.

Erin M Lloyd, Rachael C Crew, Vanessa R Haynes, Robert B White, Peter J Mark, Connie Jackaman, John M Papadimitriou, Gavin J Pinniger, Robyn M Murphy, Matthew J Watt and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Skeletal muscle, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Erin M LloydDepartment of Anatomy, Physiology and Human Biology, School of Human Sciences, The University of Western Australia, Perth, WA, Australia.
Rachael C CrewDepartment of Anatomy, Physiology and Human Biology, School of Human Sciences, The University of Western Australia, Perth, WA, Australia.
Vanessa R HaynesDepartment of Anatomy and Physiology, Faculty of Medicine Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia.
Robert B WhiteMD Education Unit, UWA Medical School, The University of Western Australia, Perth, WA, Australia.
Peter J MarkDepartment of Anatomy, Physiology and Human Biology, School of Human Sciences, The University of Western Australia, Perth, WA, Australia.
Connie JackamanCurtin Health Innovation Research Institute, Curtin Medical School, Curtin University, Bentley, WA, Australia.
John M PapadimitriouDepartment of Pathology and Laboratory Medicine, UWA Medical School, The University of Western Australia, Perth, WA, Australia.
Gavin J PinnigerDepartment of Anatomy, Physiology and Human Biology, School of Human Sciences, The University of Western Australia, Perth, WA, Australia.
Robyn M MurphyDepartment of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia.
Matthew J WattDepartment of Anatomy and Physiology, Faculty of Medicine Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia.
Miranda D GroundsDepartment of Anatomy, Physiology and Human Biology, School of Human Sciences, The University of Western Australia, Perth, WA, Australia. miranda.grounds@emeriti.uwa.edu.au.

Funding

Muscular Dystrophy Association, USA MDA418743National Health and Medical Research Council of Australia APP1077703
6 · The paper itself

Abstract

backgroundDysferlinopathies are a clinically heterogeneous group of muscular dystrophies caused by gene mutations resulting in deficiency of the membrane-associated protein dysferlin. They manifest post-growth and are characterised by muscle wasting (primarily in the limb and limb-gridle muscles), inflammation, and replacement of myofibres with adipose tissue. The precise pathomechanism for dysferlinopathy is currently unclear; as such there are no treatments currently available. Glucocorticoids (GCs) are widely used to reduce inflammation and treat muscular dystrophies, but when administered to patients with dysferlinopathy, they have unexpected adverse effects, with accelerated loss of muscle strength.

methodsTo investigate the mechanistic basis for the adverse effects of GCs in dysferlinopathy, the potent GC dexamethasone (Dex) was administered for 4-5 weeks (0.5-0.75 µg/mL in drinking water) to dysferlin-deficient BLA/J and normal wild-type (WT) male mice, sampled at 5 (Study 1) or 10 months (Study 2) of age. A wide range of analyses were conducted. Metabolism- and immune-related gene expression was assessed in psoas muscles at both ages and in quadriceps at 10 months of age. For the 10-month-old mice, quadriceps and psoas muscle histology was assessed. Additionally, we investigated the impact of Dex on the predominantly slow and fast-twitch soleus and extensor digitorum longus (EDL) muscles (respectively) in terms of contractile function, myofibre-type composition, and levels of proteins related to contractile function and metabolism, plus glycogen.

resultsAt both ages, many complement-related genes were highly expressed in BLA/J muscles, and WT mice were generally more responsive to Dex than BLA/J. The effects of Dex on BLA/J mice included (i) increased expression of inflammasome-related genes in muscles (at 5 months) and (ii) exacerbated histopathology of quadriceps and psoas muscles at 10 months. A novel observation was pronounced staining for glycogen in many myofibres of the damaged quadriceps muscles, with large pale vacuolated myofibres, suggesting possible myofibre death by oncosis.

conclusionThese pilot studies provide a new focus for further investigation into the adverse effects of GCs on dysferlinopathic muscles.

Indexed as

DexamethasoneDysferlinGlucocorticoidsMuscle, SkeletalMuscular Dystrophies, Limb-GirdleAnimalsDisease Models, AnimalMaleMembrane ProteinsMiceMuscle StrengthPilot ProjectsDexamethasoneDysferlinDysf protein, mouseGlucocorticoidsMembrane ProteinsAdipocytesComplementDexamethasoneDysferlinDysferlinopathyGlucocorticoidsGlycogenInflammasomeLimb-girdle muscular dystrophySkeletal muscle

Identifiers

PMID39123261
PMCPMC11312411

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.