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Enhanced phrenic long‐term facilitation in rats with motor neuron death from intrapleural CTB‐saporin injections (713.1)
Author(s) -
Nichols Nicole,
Mitchell Gordon
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.713.1
Subject(s) - saporin , motor neuron , medicine , respiratory system , anesthesia , neuron , intermittent hypoxia , ventilation (architecture) , biology , neuroscience , disease , immunology , immunotoxin , monoclonal antibody , antibody , obstructive sleep apnea , mechanical engineering , engineering
Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to progressive motor neuron degeneration and death by ventilatory failure. In a model of ALS (SOD1 G93A ), pLTF following acute intermittent hypoxia is enhanced at disease end‐stage by unknown mechanisms (Nichols et al., ibid , 2010). Intrapleural injections of cholera toxin B fragment conjugated to saporin (CTB‐SAP) selectively kills respiratory motor neurons and mimics motor neuron death observed in ALS rats (Nichols et al., ibid , 2013). This CTB‐SAP model allows us to study the impact of respiratory motor neuron death on breathing without many complications attendant to ALS. Here, we tested the hypothesis that phrenic motor neuron death is sufficient to enhance pLTF. pLTF was assessed in anesthetized, paralyzed and ventilated Sprague Dawley rats 7 and 28 days following bilateral intrapleural injections of: 1) CTB‐SAP (25μg), or 2) un‐conjugated CTB and SAP (control). CTB‐SAP enhanced pLTF at 7 (CTB‐SAP: 145±22%, n=10 vs . Control: 54±5%; n=15; p<0.05), but not 28 days post‐injection (CTB‐SAP: 61±14%, n=11 vs . Control: 37±9; n=5; p>0.05). Thus, pLTF at 7 (not 28) days post‐CTB‐SAP more closely resembles pLTF in end‐stage ALS rats, suggesting that processes unique to the period of active motor neuron death enhance pLTF. This project increases our understanding of respiratory plasticity and its implications for breathing in motor neuron disease. [Supported by NIH HL080209, HL69024 and the Francis Families Foundation] Grant Funding Source : Supported by NIH HL080209, HL69024 and the Francis Families Foundation