The depolarisation-induced release of [125I]BDNF from brain tissue

Androutsellis-Theotokis, Andreas; McCormack, Wendy J; Bradford, H. F.; Stern, Gerald; Pliego-Rivero, F. Bernardo

doi:10.1016/s0006-8993(96)00981-x

Cited by 40 publications

(26 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The plate was put back to the incubator, and the neurons were stimulated for 30 min with biphasic rectangular pulses delivered at various patterns (see Results). In experiments comparing the effects of patterned electrical stimulation with potassium-induced continuous depolarization, KC l was added to three additional wells, to a final concentration of 50 mM, as described previously (Ghosh et al, 1994;Androutsellis-Theotokis et al, 1996;Goodman et al, 1996;Heymach et al, 1996;Griesbeck et al, 1999;Balkowiec and Katz, 2000).…”

Section: Methodsmentioning

confidence: 99%

Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons

2002

View full text Add to dashboard Cite

Brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent modifications of neuronal connectivity and synaptic strength, including establishment of hippocampal long-term potentiation (LTP). To shed light on mechanisms underlying BDNF-dependent synaptic plasticity, the present study was undertaken to characterize release of native BDNF from newborn rat hippocampal neurons in response to physiologically relevant patterns of electrical field stimulation in culture, including tonic stimulation at 5 Hz, bursting stimulation at 25 and 100 Hz, and theta-burst stimulation (TBS). Release was measured using the ELISA in situ technique, developed in our laboratory to quantify secretion of native BDNF without the need to first overexpress the protein to nonphysiological levels. Each stimulation protocol resulted in a significant increase in BDNF release that was tetrodotoxin sensitive and occurred in the absence of glutamate receptor activation. However, 100 Hz tetanus and TBS, stimulus patterns that are most effective in inducing hippocampal LTP, were significantly more effective in releasing native BDNF than lower-frequency stimulation. For all stimulation protocols tested, removal of extracellular calcium, or blockade of N-type calcium channels, prevented BDNF release. Similarly, depletion of intracellular calcium stores with thapsigargin and treatment with dantrolene, an inhibitor of calcium release from caffeine-ryanodine-sensitive stores, markedly inhibited activity-dependent BDNF release. Our results indicate that BDNF release can encode temporal features of hippocampal neuronal activity. The dual requirement for calcium influx through N-type calcium channels and calcium mobilization from intracellular stores strongly implicates a role for calcium-induced calcium release in activity-dependent BDNF secretion.

show abstract

Section: Methodsmentioning

confidence: 99%

Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons

2002

View full text Add to dashboard Cite

show abstract

“…Activation of TTX-sensitive voltagegated Na ϩ channels has been shown in different preparations to be a prerequisite for elevated K ϩ -induced NT secretion (Blochl and Thoenen, 1995;Androutsellis-Theotokis et al, 1996;Kojima et al, 2001). We thus tested whether the postsynaptic secretion process itself requires gating of TTX-sensitive Na ϩ channels.…”

Section: Measuring Postsynaptic Secretion Of Neurotrophinsmentioning

confidence: 99%

Postsynaptic Secretion of BDNF and NT-3 from Hippocampal Neurons Depends on Calcium–Calmodulin Kinase II Signaling and Proceeds via Delayed Fusion Pore Opening

Kolarow¹,

Brigadski²,

Leßmann³

2007

J. Neurosci.

185

View full text Add to dashboard Cite

The mammalian neurotrophins (NTs) NGF, BDNF, NT-3, and NT-4 constitute a family of secreted neuronal growth factors. In addition, NTs are implicated in several forms of activity-dependent synaptic plasticity. Although synaptic secretion of NTs has been described, the intracellular signaling cascades that regulate synaptic secretion of NTs are far from being understood. Analysis of NT secretion at the subcellular level is thus required to resolve the role of presynaptic and postsynaptic NT secretion for synaptic plasticity. release from internal stores, activation of CaMKII, and intact PKA signaling, whereas Trk signaling and activation of Na ϩ channels is not required.

show abstract

“…We attempted to measure release of anterogradely transported 125 I-NT-3 directly from synaptosomes by using a conventional static release protocol (Androutsellis-Theotokis et al, 1996), with the modification that 125 I-NT-3 was loaded into tectal synaptosomes via anterograde transport from the retina in vivo. After injections of 50 -100 ng of 125 I-NT-3 into the eye, ϳ3-4 pg (450 -600 cpm) of 125 I-NT-3 was present in the synaptosomal fraction, but only a fraction of this amount (ϳ1 pg Ϸ100 -200 cpm) was recovered per tectum after washes, resuspension, and warming to 37°C.…”

Section: Direct Release From Synaptosomes Using the Conventional Assaymentioning

confidence: 99%

Mechanisms of the Release of Anterogradely Transported Neurotrophin-3 from Axon Terminals

et al. 2002

View full text Add to dashboard Cite

Neurotrophins have profound effects on synaptic function and structure. They can be derived from presynaptic, as well as postsynaptic, sites. To date, it has not been possible to measure the release of neurotrophins from axon terminals in intact tissue. We implemented a novel, extremely sensitive assay for the release and transfer of anterogradely transported neurotrophin-3 (NT-3) from a presynaptic to a postsynaptic location that uses synaptosomal fractionation after introduction of radiolabeled NT-3 into the retinotectal projection of chick embryos. Release of the anterogradely transported NT-3 in intact tissue was assessed by measuring the amount remaining in synaptosomal preparations after treatment of whole tecta with pharmacological agents. Use of this assay reveals that release of NT-3 from axon terminals is increased by depolarization, calcium influx via N-type calcium channels, and cAMP analogs, and release is most profoundly increased by excitation with kainic acid or mobilization of calcium from intracellular stores. NT-3 release depends on extracellular sodium, CaM kinase II activity, and requires intact microtubules and microfilaments. Dantrolene inhibits the high potassium-induced release of NT-3, indicating that release of calcium from intracellular stores is required. Tetanus toxin also inhibits NT-3 release, suggesting that intact synaptobrevin or synaptobrevin-like molecules are required for exocytosis. Ultrastructural autoradiography and immunolabel indicate that NT-3 is packaged in presumptive large dense-core vesicles. These data show that release of NT-3 from axon terminals depends on multiple regulatory proteins and ions, including the mobilization of local calcium. The data provide insight in the mechanisms of anterograde neurotrophins as synaptic modulators. ; presynaptic terminals; calcium; axonal transport; neurotrophin; synapse; synaptic transmission Neurotrophins are important regulators of neuronal differentiation and synaptic plasticity (Lohof et al., 1993;Snider, 1994;Kang and Schuman, 1995;Thoenen, 1995;McAllister et al., 1999;Poo, 2001). Traditionally, neurotrophins were believed to be derived by retrograde axonal transport from target cells, but recent studies revealed that neurotrophins are also transported anterogradely along axons (von Bartheld et al Key words: neurotrophic factors; secretion

show abstract

The depolarisation-induced release of [125I]BDNF from brain tissue

Cited by 40 publications

References 49 publications

Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons

Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons

Postsynaptic Secretion of BDNF and NT-3 from Hippocampal Neurons Depends on Calcium–Calmodulin Kinase II Signaling and Proceeds via Delayed Fusion Pore Opening

Mechanisms of the Release of Anterogradely Transported Neurotrophin-3 from Axon Terminals

Contact Info

Product

Resources

About