Nerve Growth Factor Modulates Synaptic Transmission between Sympathetic Neurons and Cardiac Myocytes

Lockhart, Sybil T.; Turrigiano, Gina G.; Birren, Susan J.

doi:10.1523/jneurosci.17-24-09573.1997

Cited by 139 publications

(146 citation statements)

References 80 publications

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“…In addition to the morphological long-term effects of NGF on nerve sprouting, it has also been shown that NGF modulates the function of sympathoadrenergic neurotransmission in cocultures of cardiomyocytes with neurons. 27 No data are available about the specific role of NGF on the disturbed local cardiac sympathetic nerve function in CHF.…”

Section: Discussionmentioning

confidence: 99%

Injection of Nerve Growth Factor Into Stellate Ganglia Improves Norepinephrine Reuptake Into Failing Hearts

et al. 2006

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Abstract-An impairment of cardiac norepinephrine reuptake through the neuronal norepinephrine transporter promotes depletion of cardiac norepinephrine stores and local cardiac sympathetic activation in heart failure. Nerve growth factor regulates differentiation and survival of adult sympathetic cells and is decreased in failing hearts. We hypothesized that injection of nerve growth factor into stellate ganglia normalizes cardiac norepinephrine homeostasis in experimental heart failure. Rats with transverse aortic constriction characterized by heart failure, depleted cardiac norepinephrine stores, and impaired cardiac norepinephrine reuptake were used as an experimental model. Nerve growth factor (20 g) or saline was directly injected into left stellate ganglia 4 weeks after transverse aortic constriction. Thirty-two hours after injection, determinants of cardiac norepinephrine homeostasis were measured. As compared with saline, nerve growth factor refilled depleted cardiac norepinephrine stores and improved cardiac [ 3 H]-norepinephrine uptake into isolated perfused hearts of transverse aortic constricted rats. In addition, pharmacological blockade of the norepinephrine transporter led to a higher increase in the overflow of endogenous norepinephrine from hearts of nerve growth factor-injected than saline-injected transverse aortic constricted rats. Norepinephrine transporter mRNA levels and the density of cardiac sympathetic nerves were not changed. Thirty-two hours after nerve growth factor injection, echocardiography revealed an increase in fractional shortening as compared with 2 days before injection. In conclusion, nerve growth factor attenuates local cardiac sympathetic overdrive of hypertrophic hearts by improving cardiac norepinephrine reuptake and might represent a novel therapeutic principle in the treatment of heart failure.

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Section: Discussionmentioning

confidence: 99%

Injection of Nerve Growth Factor Into Stellate Ganglia Improves Norepinephrine Reuptake Into Failing Hearts

et al. 2006

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“…SNs were prepared and cultured from newborn Sprague-Dawley rats or ETA fl/fl mice as described previously (48). Briefly, freshly isolated superior cervical ganglia from 1-to 3-d-old pups were dissected, incubated for 45 min in 1.5 mg/mL collagenase, titrated, and then preplated on cultural plastic to permit the attachment of nonneuronal cells.…”

Section: Methodsmentioning

confidence: 99%

Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling

Lehmann

Rostosky

Buss

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance In failing hearts, norepinephrine (NE) net release and endothelin-1 (ET1) levels are increased. ET1 receptor antagonists were successfully used in preclinical heart failure (HF) studies, but clinical studies did not show beneficial effects in HF patients. We found that mice lacking endothelin receptor A (ET A ) only in sympathetic neurons but not in cardiomyocytes were protected from the development of HF. Mechanistically, the presynaptic reuptake of NE within the heart was preserved in mice lacking ET A only in sympathetic neurons. These data provide an explanation of why patients in clinical studies do not benefit from ET1 receptor antagonists, because these patients are usually treated with β blockers, which interfere with the mechanism of action identified here.

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“…In vitro studies suggest an NGF effect on neuron-target connectivity In cultures of SCG neurons and ventricular myocytes from neonatal rat, NGF perfusion leads to an acute increase in the beating rate of myocytes (Lockhart et al 1997). In addition, long-term effects are observed in cocultures grown for 3 days with two NGF concentrations that both support neuronal survival.…”

Section: Ngf Availability Promotes Peripheral Innervationmentioning

confidence: 99%

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

2009

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Manipulation of neurotrophin (NT) signalling by administration or depletion of NTs, by transgenic overexpression or by deletion of genes coding for NTs and their receptors has demonstrated the importance of NT signalling for the survival and differentiation of neurons in sympathetic and dorsal root ganglia (DRG). Combination with mutation of the proapoptotic Bax gene allows the separation of survival and differentiation effects. These studies together with cell culture analysis suggest that NT signalling directly regulates the differentiation of neuron subpopulations and their integration into neural networks. The high-affinity NT receptors trkA, trkB and trkC are restricted to subpopulations of mature neurons, whereas their expression at early developmental stages largely overlaps. trkC is expressed throughout sympathetic ganglia and DRG early after ganglion formation but becomes restricted to small neuron subpopulations during embryogenesis when trkA is turned on. The temporal relationship between trkA and trkC expression is conserved between sympathetic ganglia and DRG. In DRG, NGF signalling is required not only for survival, but also for the differentiation of nociceptors. Expression of neuropeptides calcitonin gene-related peptide and substance P, which specify peptidergic nociceptors, depends on nerve growth factor (NGF) signalling. ret expression indicative of nonpeptidergic nociceptors is also promoted by the NGFsignalling pathway. Regulation of TRP channels by NGF signalling might specify the temperature sensitivity of afferent neurons embryonically. The manipulation of NGF levels "tunes" heat sensitivity in nociceptors at postnatal and adult stages. Brain-derived neurotrophic factor signalling is required for subpopulations of DRG neurons that are not fully characterized; it affects mechanical sensitivity in slowly adapting, low-threshold mechanoreceptors and might involve the regulation of DEG/ENaC ion channels. NT3 signalling is required for the generation and survival of various DRG neuron classes, in particular proprioceptors. Its importance for peripheral projections and central connectivity of proprioceptors demonstrates the significance of NT signalling for integrating responsive neurons in neural networks. The molecular targets of NT3 signalling in proprioceptor differentiation remain to be characterized. In sympathetic ganglia, NGF signalling regulates dendritic development and axonal projections. Its role in the specification of other neuronal properties is less well analysed. In vitro analysis suggests the involvement of NT signalling in the choice between the noradrenergic and cholinergic transmitter phenotype, in the expression of various classes of ion channels and for target connectivity. In vivo analysis is required to show the degree to which NT signalling regulates these sympathetic neuron properties in developing embryos and postnatally.

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Nerve Growth Factor Modulates Synaptic Transmission between Sympathetic Neurons and Cardiac Myocytes

Cited by 139 publications

References 80 publications

Injection of Nerve Growth Factor Into Stellate Ganglia Improves Norepinephrine Reuptake Into Failing Hearts

Injection of Nerve Growth Factor Into Stellate Ganglia Improves Norepinephrine Reuptake Into Failing Hearts

Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

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