Sepsis induced denervation-like changes at the neuromuscular junction

Area of Science:

• Neurology
• Pathophysiology
• Molecular Biology

Background:

• Sepsis induces significant systemic inflammation and can lead to organ dysfunction.
• The neuromuscular junction (NMJ) is crucial for motor function and can be affected by systemic diseases.
• Understanding sepsis-induced NMJ alterations is vital for managing patient recovery and mobility.

Purpose of the Study:

• To investigate the functional and biochemical alterations at the NMJ caused by sepsis.
• To compare sepsis-induced NMJ changes with those observed in denervation models.
• To elucidate the molecular mechanisms underlying sepsis-related NMJ dysfunction.

Main Methods:

• Male Sprague-Dawley rats were assigned to control, denervation, or sepsis groups.
• Sepsis was induced via cecal ligation and puncture (CLP); denervation was induced by tibialis nerve transection.
• NMJ function, end-plate area, acetylcholine receptor (AChR) levels, and neuregulin-1 expression were assessed at 1, 7, and 14 days post-procedure.

Main Results:

• Sepsis led to decreased compound muscle action potential (CMAP) amplitude and prolonged duration, alongside reduced motor conduction velocity.
• Both sepsis and denervation upregulated gamma-nicotinic acetylcholine receptors (γ-nAChR) and alpha-7-nicotinic acetylcholine receptors (α7-nAChR).
• Sepsis resulted in increased NMJ area and fragmentation, and decreased neuregulin-1 levels, mimicking denervation effects.

Conclusions:

• Chronic sepsis exerts a denervation-like effect on the NMJ.
• This effect is characterized by the upregulation of various nAChRs, enlarged end plates, and motoneuron axon demyelination.
• Sepsis-induced NMJ changes contribute to impaired neuromuscular transmission and muscle function.