PMID- 24666389 OWN - NLM STAT- MEDLINE DCOM- 20150303 LR - 20211021 IS - 1460-9568 (Electronic) IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 40 IP - 1 DP - 2014 Jul TI - Reduced levels of brain-derived neurotrophic factor contribute to synaptic imbalance during the critical period of respiratory development in rats. PG - 2183-95 LID - 10.1111/ejn.12568 [doi] AB - Previously, our electrophysiological studies revealed a transient imbalance between suppressed excitation and enhanced inhibition in hypoglossal motoneurons of rats on postnatal days (P) 12-13, a critical period when abrupt neurochemical, metabolic, ventilatory and physiological changes occur in the respiratory system. The mechanism underlying the imbalance is poorly understood. We hypothesised that the imbalance was contributed by a reduced expression of brain-derived neurotrophic factor (BDNF), which normally enhances excitation and suppresses inhibition. We also hypothesised that exogenous BDNF would partially reverse this synaptic imbalance. Immunohistochemistry/single-neuron optical densitometry, real-time quantitative PCR (RT-qPCR) and whole-cell patch-clamp recordings were done on hypoglossal motoneurons in brainstem slices of rats during the first three postnatal weeks. Our results indicated that: (1) the levels of BDNF and its high-affinity tyrosine receptor kinase B (TrkB) receptor mRNAs and proteins were relatively high during the first 1-1.5 postnatal weeks, but dropped precipitously at P12-13 before rising again afterwards; (2) exogenous BDNF significantly increased the normally lowered frequency of spontaneous excitatory postsynaptic currents but decreased the normally heightened amplitude and frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) during the critical period; (3) exogenous BDNF also decreased the normally heightened frequency of miniature IPSCs at P12-13; and (4) the effect of exogenous BDNF was partially blocked by K252a, a TrkB receptor antagonist. Thus, our results are consistent with our hypothesis that BDNF and TrkB play an important role in the synaptic imbalance during the critical period. This may have significant implications for the mechanism underlying sudden infant death syndrome. CI - (c) 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. FAU - Gao, Xiu-Ping AU - Gao XP AD - Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA. FAU - Liu, Qiuli AU - Liu Q FAU - Nair, Bindu AU - Nair B FAU - Wong-Riley, Margaret T T AU - Wong-Riley MT LA - eng GR - R01 HD048954/HD/NICHD NIH HHS/United States GR - HD048954/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140326 PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Central Nervous System Agents) RN - 0 (Indole Alkaloids) RN - 0 (RNA, Messenger) RN - 97161-97-2 (staurosporine aglycone) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Animals, Newborn MH - Brain Stem/drug effects/*growth & development/physiology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Carbazoles/pharmacology MH - Central Nervous System Agents/pharmacology MH - Excitatory Postsynaptic Potentials/drug effects/physiology MH - Female MH - Gene Expression Regulation, Developmental MH - Hypoglossal Nerve/drug effects/*growth & development/physiology MH - Indole Alkaloids/pharmacology MH - Inhibitory Postsynaptic Potentials/drug effects/physiology MH - Male MH - Miniature Postsynaptic Potentials/drug effects/physiology MH - Motor Neurons/drug effects/*physiology MH - RNA, Messenger/metabolism MH - Rats, Sprague-Dawley MH - Receptor, trkB/antagonists & inhibitors/metabolism MH - *Respiration/drug effects MH - Synapses/drug effects/*physiology MH - Tissue Culture Techniques PMC - PMC4107017 MID - NIHMS572041 OTO - NOTNLM OT - BDNF/TrkB OT - critical period OT - immunohistochemistry OT - real-time quantitative PCR OT - whole-cell patch clamp recording COIS- All authors have no conflict of interest to declare. EDAT- 2014/03/29 06:00 MHDA- 2015/03/04 06:00 PMCR- 2015/07/01 CRDT- 2014/03/27 06:00 PHST- 2013/08/27 00:00 [received] PHST- 2014/02/15 00:00 [revised] PHST- 2014/02/18 00:00 [accepted] PHST- 2014/03/27 06:00 [entrez] PHST- 2014/03/29 06:00 [pubmed] PHST- 2015/03/04 06:00 [medline] PHST- 2015/07/01 00:00 [pmc-release] AID - 10.1111/ejn.12568 [doi] PST - ppublish SO - Eur J Neurosci. 2014 Jul;40(1):2183-95. doi: 10.1111/ejn.12568. Epub 2014 Mar 26.