Denervation of neuromuscular junctions in the extensor digitorum longus of aging mice

How does the connection morphology of motor neuron axons and muscle fiber endplates change with age? Chai et al recently published some results addressing, in part, this question.

Their study compared young 3 month and geriatric 29 month old mice, which, as the authors note, correspond to roughly 20 and 80 years in humans, respectively. However, it’s always important to keep in mind that mice differ from humans in many important ways.

The researchers cut out muscle tissue, sectioned it in 20 um segments, and double stained with antibodies for both synaptophysin (to detect pre-synaptic nerve terminals) and α-bungarotoxin (to detect postsynaptic muscle endplates).

They then classified neuromuscular junctions that stained positive for both synaptophysin and α-bungarotoxin as innervated, and classified junctions positive for α-bungarotoxin only as denervated. Below is an example of a confocal image of a double stained tissue slice.

EDL = extensor digitorum longus; synaptophysin = red; α-bungarotoxin = green; overlay = yellow; white circle = example of endplate positive for only α-bungarotoxin; scale bars = 75 um; doi:10.1371/journal.pone.0028090.g002 part d-f

Across all samples analyzed, ~7 +/- 2% of neuromuscular junctions were fully denervated in 3 month old mice and ~20 +/- 3% of neuromuscular junctions were fully denervated in 29 month old mice. Such denervation could help account for any age-related decrease in muscle function.

Interestingly and importantly, the researchers did not find a similar trend in the soleus. The lack of concordance underscores some of the variability across tissues of the same type in aging.

Reference

Chai RJ, Vukovic J, Dunlop S, Grounds MD, Shavlakadze T (2011) Striking Denervation of Neuromuscular Junctions without Lumbar Motoneuron Loss in Geriatric Mouse Muscle. PLoS ONE 6(12): e28090. doi:10.1371/journal.pone.0028090