The role and mechanism of brain derived neurotrophic factor in autonomic and cardiovascular control in the nucleus tractus solitarii
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] The brainstem nucleus tractus solitarii (nTS) is the primary site at which cardiovascular afferent input is relayed to central autonomic pathways and plays a critical role in cardiovascular regulation. However, relatively little is known about mechanisms that underlie adaptation and plasticity in cardiovascular reflex circuits in the nTS. Brain derived neurotrophic factor (BDNF), a potent neuromodulator, is highly expressed within the nTS circuitry. Therefore the current studies were designed to determine if BDNF contributes to the central neural regulation of cardiovascular and autonomic function in the nTS. Findings presented in AIM 1 demonstrate that BDNF in nTS plays a novel tonic sympathoexcitatory role by modulating excitatory neurotransmission. In AIM 2 we extended our investigation to the cardiovascular disease model of the spontaneously hypertensive rat (SHR). Results from these studies demonstrate that acute removal of BDNF in the nTS of SHR reduces sympathetic overactivity and lowers blood pressure to normotensive control levels. In addition, nTS-BDNF signaling components are enhanced in the SHR. Collectively our data demonstrate a previously unrecognized role for BDNF in the central regulation of cardiovascular function. In addition, these findings raise the possibility that BDNF signaling in nTS may be a therapeutic target for regulating cardiovascular homeostasis in the setting of hypertension.
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