Inhibition of hippocampal interleukin-6 receptor-evoked signalling normalises long-term potentiation in dystrophin-deficient mice.

Duchenne muscular dystrophy (DMD), an X-linked neuromuscular disorder, characterised by progressive immobility, chronic inflammation and premature death, is caused by the loss of the mechano-transducing signalling molecule, dystrophin. In non-contracting cells, such as neurons, dystrophin is likely to have a functional role in synaptic plasticity, anchoring post-synaptic receptors. Dystrophin-expressing hippocampal neurons are key to cognitive functions such as emotions, learning and the consolidation of memories.

Astrocyte proliferation in the hippocampal dentate gyrus is suppressed across the lifespan of dystrophin-deficient mdx mice.

Absence of the structural protein, dystrophin, results in the neuromuscular disorder Duchenne Muscular Dystrophy (DMD). In addition to progressive skeletal muscle dysfunction, this multisystemic disorder can also result in cognitive deficits and behavioural changes that are likely to be consequences of dystrophin loss from central neurons and astrocytes. Dystrophin-deficient mdx mice exhibit decreases in grey matter volume in the hippocampus, the brain region that encodes and consolidates memories, and this is exacerbated with ageing.

Interleukin-6: A neuro-active cytokine contributing to cognitive impairment in Duchenne muscular dystrophy?

Interleukin-6 (IL-6) is a pro-inflammatory cytokine, classically associated with orchestrating an immune response to invading pathogens. However, IL-6 can also directly or indirectly modify central nervous system function, and thereby alter higher-order functions, such as learning and the consolidation of memories. IL-6 is chronically elevated in Duchenne Muscular Dystrophy (DMD), a neuromuscular disorder arising when a mutation causes the loss of the structural protein, dystrophin.