Format

Send to

Choose Destination
See comment in PubMed Commons below
J Neurochem. 2014 May;129(4):573-80. doi: 10.1111/jnc.12656. Epub 2014 Feb 10.

Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability.

Author information

1
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland, USA.

Abstract

Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haploinsufficiency exhibit elevated resting heart rate, and infusion of BDNF intracerebroventricularly reduces heart rate in both wild-type and BDNF+/- mice. The atropine-induced elevation of heart rate is diminished in BDNF+/- mice and is restored by BDNF infusion, whereas the atenolol-induced decrease in heart rate is unaffected by BDNF levels, suggesting that BDNF signaling enhances parasympathetic tone which is diminished with BDNF haploinsufficiency. Whole-cell recordings from pre-motor cholinergic cardioinhibitory vagal neurons in the nucleus ambiguus indicate that BDNF haploinsufficiency reduces cardioinhibitory vagal neuron activity by increased inhibitory GABAergic and diminished excitatory glutamatergic neurotransmission to these neurons. Our findings reveal a previously unknown role for BDNF in the control of heart rate by a mechanism involving increased activation of brainstem cholinergic parasympathetic neurons.

KEYWORDS:

BDNF; GABA; glutamate; nucleus ambiguus; parasympathetic; vagus nerve

PMID:
24475741
PMCID:
PMC4137462
DOI:
10.1111/jnc.12656
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center