Faculty Collaboration Database

Reduced levels of brain-derived neurotrophic factor contribute to synaptic imbalance during the critical period of respiratory development in rats. Eur J Neurosci 2014 Jul;40(1):2183-95

Date

03/29/2014

Pubmed ID

24666389

Pubmed Central ID

PMC4107017

DOI

10.1111/ejn.12568

Scopus ID

2-s2.0-84903882766 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

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.

Author List

Gao XP, Liu Q, Nair B, Wong-Riley MT

MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Brain Stem
Brain-Derived Neurotrophic Factor
Carbazoles
Central Nervous System Agents
Excitatory Postsynaptic Potentials
Female
Gene Expression Regulation, Developmental
Hypoglossal Nerve
Indole Alkaloids
Inhibitory Postsynaptic Potentials
Male
Miniature Postsynaptic Potentials
Motor Neurons
RNA, Messenger
Rats, Sprague-Dawley
Receptor, trkB
Respiration
Synapses
Tissue Culture Techniques