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Adenosine 2A (A 2A ) receptor expression in rats with motor neuron death from intrapleural CTB‐saporin injections
Author(s) -
Craig Taylor A.,
Brown Scott M.,
Nichols Nicole L.
Publication year - 2017
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.31.1_supplement.873.14
Subject(s) - saporin , phrenic nerve , receptor , motor neuron , downregulation and upregulation , tropomyosin receptor kinase b , cholera toxin , neuron , medicine , chemistry , biology , anesthesia , neuroscience , respiratory system , spinal cord , immunology , biochemistry , neurotrophic factors , immunotoxin , monoclonal antibody , gene , antibody
When injected intrapleurally, cholera toxin B fragment conjugated to saporin (CTB‐SAP) mimics aspects of ALS including the amount of phrenic motor neuron death observed in ALS rats (Nichols et al., 2015). This selective phrenic motor neuron death is sufficient to enhance phrenic long‐term facilitation (pLTF, a form of phrenic motor facilitation; Nichols and Mitchell, ibid , 2014) after 7, not 28, days of CTB‐SAP. pLTF in normal rats predominately requires 5HT 2 receptors and the new synthesis of BDNF, although there is an alternative BDNF independent mechanism for pLTF that requires A 2A receptors and the new synthesis of TrkB. Preliminary data suggest that the mechanism responsible for pLTF following 7 days of 25mg CTB‐SAP is TrkB dependent (Nichols et al. ibid ). Here, we tested the hypothesis that A 2A receptor expression is upregulated on phrenic motor neurons following 7, not 28 days, of 25mg CTB‐SAP using immunohistochemistry. A 2A receptor expression was studied in Sprague Dawley rats 7 and 28 days following bilateral intrapleural injections of: 1) CTB‐SAP (25μg), or 2) un‐conjugated CTB and SAP (control). Our preliminary data suggest that following CTB‐SAP injection, total A 2A receptor positive pixels appear to be increased in the phrenic motor nucleus and non‐phrenic ventral horn at 7 (82±45 and 93±55 pixels, respectively; n=9), not 28 (8 and 8 pixels, respectively; n=2), days later vs . controls (51±24 and 27±15 pixels, respectively; n=6). This suggests that A 2A receptors are upregulated to enhance pLTF at 7, not 28, days post‐CTB‐SAP. Future studies will be focused on completing this histology analysis and testing whether pLTF in 7, not 28, day CTB‐SAP treated rats is abolished following C 4 intrathecal, A 2A receptor antagonist treatment. This project increases our understanding of the expression of receptors associated with respiratory plasticity and its implications for breathing following motor neuron death. Support or Funding Information Supported by NIH K99/R00 HL119606