#apaperaday: Abnormal Expression of Synaptic and Extrasynaptic GABAA Receptor Subunits in the Dystrophin-Deficient mdx Mouse

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Abnormal Expression of Synaptic and Extrasynaptic GABAA Receptor Subunits in the dystrophin-Deficient mdx Mouse

Today’s pick is on Duchenne and the brain to get into the brain mood. Paper is by Zarrouki et al in Int journal of molecular sciences doi 10.3390/ijms232012617. Duchenne is known mostly for its muscle involvement but dystrophin is also expressed in the brain and many Duchenne patients have learning difficulties and behavioral problems.

In the brain full length dystrophin is involved in clustering subunits of GABAa receptors. These receptors are involved in brain connectivity, activity and plasticity. Here authors wanted to study in detail how lack of full length dystrophin affects subunit formation in mouse brain.

Pet imaging showed no macroscopic changes between mdx (no full length dystrophin) and wild type mice. Western blotting revealed a different composition of subunits in brain regions. It also showed gabaa receptor subunit expression is lower in the spinal cord than brain.

I am not a brain person but I get a few take home lessons from this paper: lack of dystrophin has different effects on GABAa receptor subunit clustering in different brain regions. Earlier work from authors show this can normalize upon dystrophin restoration in mice.

Another point authors make is that loss of muscle and muscle denervation may have an impact on the peripheral nervous system. This is not well studied but I like this comment because muscle is connected to the brain. Need to look also holistically.I refer brain experts to read the paper as I probably did not do it justice. Clearly more work is needed (in mouse and human) which is ongoing e.g. through the BIND project in which some of these authors are involved as well.