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Inflammation Enhances Spinal BDNF‐Induced Phrenic Motor Facilitation
Author(s) -
Agosto Ibis,
Mitchell Gordon
Publication year - 2015
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.29.1_supplement.659.11
Subject(s) - tropomyosin receptor kinase b , intermittent hypoxia , brain derived neurotrophic factor , medicine , inflammation , phrenic nerve , neurotrophic factors , facilitation , spinal cord , anesthesia , receptor , respiratory system , neuroscience , biology , psychiatry , obstructive sleep apnea
Long‐lasting phrenic motor facilitation (pMF) can be elicited by multiple, distinct cellular mechanisms. For example, acute intermittent hypoxia triggers a form of pMF known as phrenic long‐term facilitation (pLTF); pLTF requires new synthesis of brain derived neurotrophic factor (BDNF) and activation of its high affinity receptor (TrkB) in the cervical spinal cord (Baker‐Herman et al. 2004). Since systemic inflammation abolishes AIH‐induced pLTF (Huxtable et al. 2013), we tested the hypothesis that the functional impairment is upstream from BDNF/TrkB signaling by testing the impact of systemic inflammation on pMF elicited by cervical spinal injections of BDNF. We assessed phrenic nerve activity before and after intrathecal C4 BDNF (100ng, 12uL) injections in anesthetized, paralyzed and ventilated adult rats 24 hrs post‐LPS (100ug/kg, i.p.) or control (saline) injections. To our surprise, LPS pretreatment enhanced BDNF‐induced pMF (LPS: 105% baseline; versus control: 58% baseline; both n=4; p < 0.05). These results enable two Conclusions 1) LPS induced inflammation most likely impairs AIH‐induced pLTF upstream from BDNF/TrkB signaling; and 2) unknown downstream mechanisms attempt to compensate, enhancing the BDNF/TrkB induced pMF. These conclusions advance our understanding concerning the impact of even mild inflammation on important forms of spinal respiratory motor plasticity. [Supported by: NIH HL111598]