Daily intermittent hypoxia augments spinal BDNF levels, ERK phosphorylation and respiratory long-term facilitation.
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.
Wilkerson
Julia E R
JE
Department of Comparative Biosciences, University of Wisconsin, School of Veterinary Medicine, Madison, WI 53706, USA.
Mitchell
Gordon S
GS
D000818:Animals; D001784:Blood Gas Analysis / Q000379:methods; D001794:Blood Pressure; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007002:Hypoglossal Nerve / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D010766:Phosphorylation / Q000502:physiology; D010791:Phrenic Nerve / Q000503:physiopathology; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D012119:Respiration; D013116:Spinal Cord / Q000378:metabolism*; D013997:Time Factors; D014628:Vagotomy / Q000379:methods
D019208:Brain-Derived Neurotrophic Factor; D048049:Extracellular Signal-Regulated MAP Kinases