In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in mdx Mouse.
Today’s pick is again Duchenne themed for the Duchenne Patient Academy still occurring in Rome. It is from the journal Life by Moritti et al doi 10.3390/life13222861
The topic is outside my direct area of expertise: the neuromuscular junction and acetylcholine receptor development in very young mdx and wild type muscles. Dystrophin is expressed in muscle and brain (see yesterday #apaperaday). However it is also located in the muscle endplate (connection between motor neuron and muscle). It binds voltage gated channels. Utrophin is present in neuromuscular junctions (NMJ, the nerve side of the connection) and clusters acetylcholine receptors.
In mdx mice and Duchenne patients NMJ abnormalities have been observed. The endplate is fragmented which makes communication from motor neuron to muscle more difficult and leads to weakness.
The question is whether these abnormalities are because of lack of dystrophin or because of denervation of muscles due to muscle damage. Authors here studied this by analyzing very young mouse muscles. Here NMJs are still developing and there is no muscle damage yet. Authors studied the digitorum brevis muscle in mdx and wild type mice age 7, 11, 14 and 21 days. These are very small mice and the digitorum brevis is small to begin with so kudos for succeeding in this technical challenge.
Authors analyzed 150 fibers in mdx and wild type combined and showed that the timing of innervation is the same. Also the location (endplate vs extra-synaptic) were the same. However the frequency of channels opening differed. This decreased with aging/maturation in wild type mice, while it stayed constant or increased in mdx mice. Mdx had more high activity fibers. This suggests a problem with maturation.
Authors stained NMJs with alphabungarotoxin in tibialis anterior of mdx & wild type but saw no fragmented endplates. Authors discuss the difference in high activity fibres & frequency of channel opening could be due to problems with acetylcholine receptor aggregation in mdx mice.
They conclude that more work is needed to elucidate things more fully. For the original question (are problems due to damage/denervation or loss of dystrophin) I think the answer is yes to both. So not OR but AND. This makes researching this more challenging but that is something the Duchenne field is used to!