BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia.
Intermittent hypoxia causes a form of serotonin-dependent synaptic plasticity in the spinal cord known as phrenic long-term facilitation (pLTF). Here we show that increased synthesis of brain-derived neurotrophic factor (BDNF) in the spinal cord is necessary and sufficient for pLTF in adult rats. We found that intermittent hypoxia elicited serotonin-dependent increases in BDNF synthesis in ventral spinal segments containing the phrenic nucleus, and the magnitude of these BDNF increases correlated with pLTF magnitude. We used RNA interference (RNAi) to interfere with BDNF expression, and tyrosine kinase receptor inhibition to block BDNF signaling. These disruptions blocked pLTF, whereas intrathecal injection of BDNF elicited an effect similar to pLTF. Our findings demonstrate new roles and regulatory mechanisms for BDNF in the spinal cord and suggest new therapeutic strategies for treating breathing disorders such as respiratory insufficiency after spinal injury. These experiments also illustrate the potential use of RNAi to investigate functional consequences of gene expression in the mammalian nervous system in vivo.
Baker-Herman
Tracy L
TL
Department of Comparative Biosciences, University of Wisconsin, Madison, Wisconsin 53706, USA.
Fuller
David D
DD
Bavis
Ryan W
RW
Zabka
Andrea G
AG
Golder
Francis J
FJ
Doperalski
Nicholas J
NJ
Johnson
Rebecca A
RA
Watters
Jyoti J
JJ
Mitchell
Gordon S
GS
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D010791:Phrenic Nerve / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D013116:Spinal Cord / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor