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Author Spotlight: Studying Neuromuscular Responses and Motor Neuron Plasticity in Neurodegenerative Diseases
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Adenosine-dependent phrenic motor facilitation is inflammation resistant.
Ibis M Agosto-Marlin1, Nicole L Nichols1, Gordon S Mitchell2,3
1Department of Comparative Biosciences, University of Wisconsin, Madison, Wisconsin; and.
Journal of Neurophysiology
|December 9, 2016
Summary
Severe acute intermittent hypoxia (sAIH) induces phrenic motor facilitation (pMF) via an adenosine-dependent pathway that remains functional despite mild systemic inflammation. This adenosine pathway acts as a backup for respiratory plasticity when other mechanisms are suppressed.
Area of Science:
- Neuroscience
- Respiratory Physiology
- Neuroplasticity
Background:
- Phrenic motor facilitation (pMF) is a form of respiratory plasticity.
- Moderate acute intermittent hypoxia (mAIH) induces pMF via a serotonin-dependent pathway, which is blocked by systemic inflammation (lipopolysaccharide, LPS).
- Severe acute intermittent hypoxia (sAIH) induces pMF via a different, adenosine-dependent pathway.
Purpose of the Study:
- To test if sAIH-induced pMF and adenosine 2A (A2A) receptor-induced pMF are insensitive to mild systemic inflammation.
- To investigate the functional significance of multiple cascades in phrenic motor plasticity.
- To determine if the adenosine-dependent pathway serves as a backup mechanism for pMF.
Main Methods:
- Systemic administration of lipopolysaccharide (LPS) to induce mild inflammation.
- Induction of pMF using severe acute intermittent hypoxia (sAIH) or direct A2A receptor agonist (CGS-21680) application.
- Assessment of pMF 24 hours post-LPS exposure.
- Blockade of sAIH-induced pMF using an A2A receptor antagonist (MSX-3) to confirm adenosine dependence.
Main Results:
- sAIH-induced pMF and A2A receptor agonist-induced pMF were not affected by LPS-induced systemic inflammation.
- Intrathecal A2A receptor antagonist administration blocked sAIH-induced pMF 24 hours post-LPS, confirming adenosine dependence.
- These findings highlight the differential impact of systemic inflammation on various pMF pathways.
Conclusions:
- The adenosine-dependent pathway for phrenic motor facilitation is resistant to mild systemic inflammation.
- This adenosine-dependent mechanism represents a potential 'backup' system for respiratory plasticity.
- This backup system is crucial when serotonin-dependent pathways are suppressed by inflammation or neural injury.
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