Daily intermittent hypoxia augments spinal BDNF levels, ERK phosphorylation and respiratory long-term facilitation

Exp Neurol. 2009 May;217(1):116-23. doi: 10.1016/j.expneurol.2009.01.017. Epub 2009 Feb 3.

Abstract

Acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). We hypothesized that: 1) daily AIH (dAIH) preconditioning enhances phrenic and hypoglossal (XII) LTF in a rat strain with low constitutive LTF expression; 2) dAIH induces brain-derived neurotrophic factor (BDNF), a critical protein for phrenic LTF (pLTF) in the cervical spinal cord; and 3) dAIH increases post-AIH extracellular regulated kinase (ERK) activation. Phrenic and XII motor output were monitored in anesthetized dAIH- or sham-treated Brown Norway rats with and without acute AIH. pLTF was observed in both sham (18+/-9% baseline; 60 min post-hypoxia; p<0.05; n=18) and dAIH treated rats (37+/-8%; p<0.05; n=14), but these values were not significantly different (p=0.13). XII LTF was not observed in sham-treated rats (4+/-5%), but was revealed in dAIH pretreated rats (48+/-18%; p<0.05). dAIH preconditioning increased basal ventral cervical BDNF protein levels (24+/-8%; p<0.05), but had no significant effect on ERK phosphorylation. AIH increased BDNF in sham (25+/-8%; p<0.05), but not dAIH-pretreated rats (-7+/-4%), and had complex effects on ERK phosphorylation (ERK2 increased in shams whereas ERK1 increased in dAIH-treated rats). Thus, dAIH elicits metaplasticity in LTF, revealing XII LTF in a rat strain with no constitutive XII LTF expression. Increased BDNF synthesis may no longer be necessary for phrenic LTF following dAIH preconditioning since BDNF concentration is already elevated.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Gas Analysis / methods
  • Blood Pressure
  • Body Mass Index
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Hypoglossal Nerve / physiopathology
  • Hypoxia* / metabolism
  • Hypoxia* / pathology
  • Hypoxia* / physiopathology
  • Long-Term Potentiation / physiology*
  • Male
  • Phosphorylation / physiology
  • Phrenic Nerve / physiopathology
  • Radioimmunoassay / methods
  • Rats
  • Respiration*
  • Spinal Cord / metabolism*
  • Time Factors
  • Vagotomy / methods

Substances

  • Brain-Derived Neurotrophic Factor
  • Extracellular Signal-Regulated MAP Kinases