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

Julia E R Wilkerson, Gordon S. Mitchell

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)116-123
Number of pages8
JournalExperimental Neurology
Issue number1
StatePublished - May 2009


  • Brain derived neurotrophic factor
  • Extracellular regulated kinase
  • Hypoglossal
  • Intermittent hypoxia
  • Metaplasticity
  • Phrenic
  • Respiratory plasticity

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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