PMID- 29802680 OWN - NLM STAT- MEDLINE DCOM- 20190610 LR - 20240318 IS - 2051-817X (Electronic) IS - 2051-817X (Linking) VI - 6 IP - 10 DP - 2018 May TI - Brain-derived neurotrophic factor acts at neurons of the subfornical organ to influence cardiovascular function. PG - e13704 LID - 10.14814/phy2.13704 [doi] LID - e13704 AB - Brain-derived neurotrophic factor (BDNF), a neurotrophin traditionally associated with neural plasticity, has more recently been implicated in fluid balance and cardiovascular regulation. It is abundantly expressed in both the central nervous system (CNS) and peripheral tissue, and is also found in circulation. Studies suggest that circulating BDNF may influence the CNS through actions at the subfornical organ (SFO), a circumventricular organ (CVO) characterized by the lack of a normal blood-brain barrier (BBB). The SFO, well-known for its involvement in cardiovascular regulation, has been shown to express BDNF mRNA and mRNA for the TrkB receptor at which BDNF preferentially binds. This study was undertaken to determine if: (1) BDNF influences the excitability of SFO neurons in vitro; and (2) the cardiovascular consequences of direct administration of BDNF into the SFO of anesthetized rats. Electrophysiological studies revealed that bath application of BDNF (1 nmol/L) influenced the excitability of the majority of neurons (60%, n = 13/22), the majority of which exhibited a membrane depolarization (13.8 +/- 2.5 mV, n = 9) with the remaining affected cells exhibiting hyperpolarizations (-11.1 +/- 2.3 mV, n = 4). BDNF microinjections into the SFO of anesthetized rats caused a significant decrease in blood pressure (mean [area under the curve] AUC = -364.4 +/- 89.0 mmHg x sec, n = 5) with no effects on heart rate (mean AUC = -12.2 +/- 3.4, n = 5). Together these observations suggest the SFO to be a CNS site at which circulating BDNF could exert its effects on cardiovascular regulation. CI - (c) 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. FAU - Black, Emily A E AU - Black EAE AD - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada. FAU - Smith, Pauline M AU - Smith PM AD - Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada. FAU - McIsaac, William AU - McIsaac W AD - Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada. FAU - Ferguson, Alastair V AU - Ferguson AV AD - Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada. LA - eng GR - Canadian Institutes of Health Research/International PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Physiol Rep JT - Physiological reports JID - 101607800 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Action Potentials/drug effects MH - Animals MH - Blood Pressure/*drug effects MH - Brain-Derived Neurotrophic Factor/administration & dosage/*physiology MH - Heart Rate/*drug effects MH - Male MH - Neurons/drug effects/*physiology MH - Rats, Sprague-Dawley MH - Subfornical Organ/drug effects/*physiology PMC - PMC5974716 OTO - NOTNLM OT - blood pressure OT - patch clamp OT - subfornical organ EDAT- 2018/05/29 06:00 MHDA- 2019/06/14 06:00 PMCR- 2018/05/20 CRDT- 2018/05/27 06:00 PHST- 2018/04/13 00:00 [received] PHST- 2018/04/17 00:00 [accepted] PHST- 2018/05/27 06:00 [entrez] PHST- 2018/05/29 06:00 [pubmed] PHST- 2019/06/14 06:00 [medline] PHST- 2018/05/20 00:00 [pmc-release] AID - PHY213704 [pii] AID - 10.14814/phy2.13704 [doi] PST - ppublish SO - Physiol Rep. 2018 May;6(10):e13704. doi: 10.14814/phy2.13704.