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The baroreflex desensitization in CHF is at least partly the result of central neuronal network dysfunction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The dorsal medial nucleus tractus solitarius (dmNTS) has long been appreciated as a primary site of baroreceptor afferent termination in the central nervous system. However, the influence of neurotransmitters and neuromodulators in the dmNTS on baroreflex function both in normal and CHF states is not fully understood.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The present study provides the first evidence showing a tonic sympatho\u2010inhibitory role for brain\u2010derived neurotrophic factor (BDNF) neurotransmission in the dmNTS. Most importantly, BDNF\u2010 tyrosine receptor kinase B (TrkB) signalling in the dmNTS is integral for normal baroreflex function as indicated by the blunting of baroreflex sensitivity (BRS) following the antagonization of TrkB, which inhibited baroreflex gain and range.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Furthermore, we found that the tonic sympatho\u2010inhibition of BDNF was withdrawn in the CHF state, thus contributing to the increased sympathetic tone associated with CHF. Consistent with this finding, BDNF\/TrkB antagonism had little effect on reducing BRS in CHF animals, which is corroborated by the observation of decreased TrkB expression in the dmNTS during CHF. Taken together, these results implicate a reduction in BDNF\u2010TrkB signalling in the dmNTS during CHF that contributes to sympatho\u2010excitation and baroreflex desensitization.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The observation that the BDNF\/TrkB pathway is impaired in the dmNTS during CHF provides a novel mechanism for understanding the central alterations that contribute to baroreflex desensitization during CHF.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Chronic heart failure (CHF) results in blunting of arterial baroreflex sensitivity (BRS), which arises from alterations to both peripheral baroreceptors and central autonomic nuclei such as the nucleus tractus solitarius (NTS). Although glutamate is known to be an important neurotransmitter released from baroreceptor afferent synapses in the NTS, the influence of other neurotransmitters and neuromodulators remains unclear. Alterations to NTS signalling in CHF remain particularly undefined. The present study aimed to evaluate the role of brain\u2010derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) receptor signalling in the NTS on baroreflex control both in healthy and CHF rats. To this end, we microinjected BDNF or the highly selective TrkB receptor antagonist [<jats:italic>N<\/jats:italic>2\u20102\u20102\u2010oxoazepan\u20103\u2010yl amino] carbonyl phenyl benzo (b)thiophene\u20102\u2010carboxamide (ANA\u201012) into the dorsal medial NTS (dmNTS) of male Sprague\u2013Dawley rats with coronary artery ligation\u2010induced CHF and sham operated controls and recorded blood pressure and renal sympathetic nerve activity responses. We subsequently measured BRS before and after bilateral dmNTS microinjections of ANA\u201012. In sham rats, BDNF evoked a dose\u2010dependent depressor and sympatho\u2010inhibitory effect and ANA\u201012 produced the opposite response. Both of these responses were significantly blunted in CHF rats. Furthermore, bilateral microinjection of ANA\u201012 into the dmNTS greatly diminished baroreflex sensitivity in sham rats, whereas it had less of an effect in CHF rats. We observed decreased levels of TrkB protein and mRNA in the dmNTS of CHF rats. These data indicate that endogenous BDNF signalling in the NTS is integral for the maintenance of BRS and that BDNF\/TrkB signalling is impaired in the NTS in the CHF state.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp272318","type":"journal-article","created":{"date-parts":[[2016,5,6]],"date-time":"2016-05-06T09:43:38Z","timestamp":1462527818000},"page":"5711-5725","source":"Crossref","is-referenced-by-count":27,"title":["Influence of brain\u2010derived neurotrophic factor\u2010tyrosine receptor kinase B signalling in the nucleus tractus solitarius on baroreflex sensitivity in rats with chronic heart failure"],"prefix":"10.1113","volume":"594","author":[{"given":"Bryan K.","family":"Becker","sequence":"first","affiliation":[{"name":"Department of Cellular and Integrative Physiology University of Nebraska Medical Center  Omaha NE USA"},{"name":"Department of Nephrology\/Cardio\u2010Renal Physiology and Medicine University of Alabama at Birmingham  Birmingham AL 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