PMID- 30129982 OWN - NLM STAT- MEDLINE DCOM- 20190930 LR - 20200930 IS - 1365-2826 (Electronic) IS - 0953-8194 (Print) IS - 0953-8194 (Linking) VI - 30 IP - 11 DP - 2018 Nov TI - High salt loading increases brain derived neurotrophic factor in supraoptic vasopressin neurones. PG - e12639 LID - 10.1111/jne.12639 [doi] AB - High salt loading (SL) is associated with inappropriate arginine vasopressin (AVP) release and increased mean arterial pressure. Previous work has shown that chronic high salt intake impairs baroreceptor inhibition of rat AVP neurones through brain-derived neurotrophic factor (BDNF) dependent activation of tyrosine receptor kinase B (TrkB) and down-regulation of K+/Cl- co-transporter KCC2. This mechanism diminishes the GABA(A) inhibition of AVP neurones in the supraoptic nucleus (SON) by increasing intracellular chloride. However, the source of BDNF leading to this ionic plasticity is unknown. In the present study, we used adeno-associated viral vectors with short hairpin RNA against BDNF to test whether SON is the source of BDNF contributing to increased AVP release and elevated mean arterial pressure in high salt loaded rats. Virally mediated BDNF knockdown (shBDNF) in the SON of salt loaded rats significantly blocked the increases in BDNF mRNA and AVP heterogeneous RNA expression. The observed increase in the activation of TrkB receptor during salt loading is consistent with previous studies. Western blot analysis of SON punches revealed that tyrosine phosphorylation of TrkB (pTrkBY515) was significantly decreased in salt shBDNF rats compared to the salt scrambled (SCR) rats. Injections of shBDNF in the SON also significantly prevented the increase in plasma AVP concentration associated with salt loading. However, the salt loading induced increase in mean arterial pressure was not decreased with BDNF knockdown in the SON. Average daily fluid intake and urine output were significantly elevated in both salt SCR and salt shBDNF rats compared to the euhydrated controls. Daily average urine sodium concentration was significantly higher in shBDNF injected salt rats than the other groups. These findings indicate that BDNF produced in the SON contributes to the increased AVP secretion during high salt loading but not with respect to the subsequent increase in mean arterial pressure. CI - (c) 2018 British Society for Neuroendocrinology. FAU - Balapattabi, Kirthikaa AU - Balapattabi K AD - Department of Physiology and Anatomy, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas. FAU - Little, Joel T AU - Little JT AD - Department of Physiology and Anatomy, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas. FAU - Farmer, George E AU - Farmer GE AD - Department of Physiology and Anatomy, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas. FAU - Cunningham, J Thomas AU - Cunningham JT AUID- ORCID: 0000-0001-8859-9481 AD - Department of Physiology and Anatomy, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas. LA - eng GR - R01 HL119458/HL/NHLBI NIH HHS/United States GR - R01 HL142341/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20181014 PL - United States TA - J Neuroendocrinol JT - Journal of neuroendocrinology JID - 8913461 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 113-79-1 (Arginine Vasopressin) RN - 451W47IQ8X (Sodium Chloride) RN - 9NEZ333N27 (Sodium) RN - EC 2.7.10.1 (Ntrk2 protein, rat) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Arginine Vasopressin/*metabolism MH - Arterial Pressure MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Eating MH - Gene Expression MH - Heart Rate MH - Male MH - Neurons/drug effects/*metabolism MH - Rats, Sprague-Dawley MH - Receptor, trkB/metabolism MH - Sodium/urine MH - Sodium Chloride/*administration & dosage MH - Supraoptic Nucleus/drug effects/*metabolism PMC - PMC6645701 MID - NIHMS1036767 OTO - NOTNLM OT - BDNF OT - SON OT - salt loading and MNCs OT - vasopressin COIS- CONFLICT OF INTERESTS The authors declare that they have no conflicts of interest. EDAT- 2018/08/22 06:00 MHDA- 2019/10/01 06:00 PMCR- 2019/11/01 CRDT- 2018/08/22 06:00 PHST- 2018/06/22 00:00 [received] PHST- 2018/08/07 00:00 [revised] PHST- 2018/08/16 00:00 [accepted] PHST- 2018/08/22 06:00 [pubmed] PHST- 2019/10/01 06:00 [medline] PHST- 2018/08/22 06:00 [entrez] PHST- 2019/11/01 00:00 [pmc-release] AID - 10.1111/jne.12639 [doi] PST - ppublish SO - J Neuroendocrinol. 2018 Nov;30(11):e12639. doi: 10.1111/jne.12639. Epub 2018 Oct 14.