共查询到20条相似文献,搜索用时 15 毫秒
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Hui Lu Hyungju Park Mu-Ming Poo 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2014,369(1633)
In acute hippocampal slices, we found that the presence of extracellular brain-derived neurotrophic factor (BDNF) is essential for the induction of spike-timing-dependent long-term potentiation (tLTP). To determine whether BDNF could be secreted from postsynaptic dendrites in a spike-timing-dependent manner, we used a reduced system of dissociated hippocampal neurons in culture. Repetitive pairing of iontophoretically applied glutamate pulses at the dendrite with neuronal spikes could induce persistent alterations of glutamate-induced responses at the same dendritic site in a manner that mimics spike-timing-dependent plasticity (STDP)—the glutamate-induced responses were potentiated and depressed when the glutamate pulses were applied 20 ms before and after neuronal spiking, respectively. By monitoring changes in the green fluorescent protein (GFP) fluorescence at the dendrite of hippocampal neurons expressing GFP-tagged BDNF, we found that pairing of iontophoretic glutamate pulses with neuronal spiking resulted in BDNF secretion from the dendrite at the iontophoretic site only when the glutamate pulses were applied within a time window of approximately 40 ms prior to neuronal spiking, consistent with the timing requirement of synaptic potentiation via STDP. Thus, BDNF is required for tLTP and BDNF secretion could be triggered in a spike-timing-dependent manner from the postsynaptic dendrite. 相似文献
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The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function 总被引:54,自引:0,他引:54
Egan MF Kojima M Callicott JH Goldberg TE Kolachana BS Bertolino A Zaitsev E Gold B Goldman D Dean M Lu B Weinberger DR 《Cell》2003,112(2):257-269
Brain-derived neurotrophic factor (BDNF) modulates hippocampal plasticity and hippocampal-dependent memory in cell models and in animals. We examined the effects of a valine (val) to methionine (met) substitution in the 5' pro-region of the human BDNF protein. In human subjects, the met allele was associated with poorer episodic memory, abnormal hippocampal activation assayed with fMRI, and lower hippocampal n-acetyl aspartate (NAA), assayed with MRI spectroscopy. Neurons transfected with met-BDNF-GFP showed lower depolarization-induced secretion, while constitutive secretion was unchanged. Furthermore, met-BDNF-GFP failed to localize to secretory granules or synapses. These results demonstrate a role for BDNF and its val/met polymorphism in human memory and hippocampal function and suggest val/met exerts these effects by impacting intracellular trafficking and activity-dependent secretion of BDNF. 相似文献
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Santi S Cappello S Riccio M Bergami M Aicardi G Schenk U Matteoli M Canossa M 《The EMBO journal》2006,25(18):4372-4380
Regulation of brain-derived neurotrophic factor (BDNF) secretion plays a critical role in long-term potentiation (LTP). It is generally thought that the supply for this secretion is newly synthesized BDNF targeted to the synapse. Here we provide evidence that hippocampal neurons additionally recycle BDNF for activity-dependent secretion. Exogenously applied BDNF is internalized by cultured neurons and rapidly becomes available for activity-dependent secretion, which is controlled by the same mechanisms that regulate the secretion of newly synthesized BDNF. Moreover, BDNF recycling replaced the new synthesis pathway in mediating the maintenance of LTP in hippocampal slices: the late phase LTP, which is abolished by protein synthesis inhibition, was rescued in slices preincubated with BDNF. Thus, endocytosed BDNF is fed back to the activity-dependent releasable pool required for LTP maintenance. 相似文献
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Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses. 总被引:10,自引:0,他引:10
The protein brain-derived neurotrophic factor (BDNF) has been postulated to be a retrograde or paracrine synaptic messenger in long-term potentiation and other forms of activity-dependent synaptic plasticity. Although crucial for this concept, direct evidence for the activity-dependent synaptic release of BDNF is lacking. Here we investigate secretion of BDNF labelled with green fluorescent protein (BDNF-GFP) by monitoring the changes in fluorescence intensity of dendritic BDNF-GFP vesicles at glutamatergic synaptic junctions of living hippocampal neurons. We show that high-frequency activation of glutamatergic synapses triggers the release of BDNF-GFP from synaptically localized secretory granules. This release depends on activation of postsynaptic ionotropic glutamate receptors and on postsynaptic Ca(2+) influx. Release of BDNF-GFP is also observed from extrasynaptic dendritic vesicle clusters, suggesting that a possible spatial restriction of BDNF release to specific synaptic sites can only occur if the postsynaptic depolarization remains local. These results support the concept of BDNF being a synaptic messenger of activity-dependent synaptic plasticity, which is released from postsynaptic neurons. 相似文献
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Kuczewski N Fuchs C Ferrand N Jovanovic JN Gaiarsa JL Porcher C 《Journal of neurochemistry》2011,118(4):533-545
Recent studies have shown that GABA(B) receptors play more than a classical inhibitory role and can function as an important synaptic maturation signal early in life. In a previous study, we reported that GABA(B) receptor activation triggers secretion of brain-derived neurotrophic factor (BDNF) and promotes the functional maturation of GABAergic synapses in the developing rat hippocampus. To identify the signalling pathway linking GABA(B) receptor activation to BDNF secretion in these cells, we have now used the phosphorylated form of the cAMP response element-binding protein as a biological sensor for endogenous BDNF release. In the present study, we show that GABA(B) receptor-induced secretion of BDNF relies on the activation of phospholipase C, followed by the formation of diacylglycerol, activation of protein kinase C, and the opening of L-type voltage-dependent Ca(2+) channels. We further show that once released by GABA(B) receptor activation, BDNF increases the membrane expression of β(2/3) -containing GABA(A) receptors in neuronal cultures. These results reveal a novel function of GABA(B) receptors in regulating the expression of GABA(A) receptor through BDNF-tropomyosin-related kinase B receptor dependent signalling pathway. 相似文献
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Sorting and activity-dependent secretion of BDNF require interaction of a specific motif with the sorting receptor carboxypeptidase e 总被引:7,自引:0,他引:7
Activity-dependent secretion of BDNF is important in mediating synaptic plasticity, but how it is achieved is unclear. Here we uncover a sorting motif receptor-mediated mechanism for regulated secretion of BDNF. X-ray crystal structure analysis revealed a putative sorting motif, I(16)E(18)I(105)D(106), in BDNF, which when mutated at the acidic residues resulted in missorting of proBDNF to the constitutive pathway in AtT-20 cells. A V20E mutation to complete a similar motif in NGF redirected a significant proportion of it from the constitutive to the regulated pathway. Modeling and binding studies showed interaction of the acidic residues in the BDNF motif with two basic residues in the sorting receptor, carboxypeptidase E (CPE). (35)S labeling experiments demonstrated that activity-dependent secretion of BDNF from cortical neurons was obliterated in CPE knockout mice. Thus, we have identified a mechanism whereby a specific motif I(16)E(18)I(105)D(106) interacts with CPE to sort proBDNF into regulated pathway vesicles for activity-dependent secretion. 相似文献
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BDNF与抑郁症的研究现状及进展 总被引:2,自引:0,他引:2
脑源性神经营养因子(brain-derived neurothrophic factor,BDNF)在中枢和外周均广泛存在,基于对其神经再生和修复功能的普遍认识,越来越多的研究开始关注BDNF在抑郁发生过程中对神经可塑性的影响以及BDNF在抗抑郁药物治疗中发挥的作用.本文综述了BDNF与抑郁症关系的基础性研究成果,以及近两年的相关研究趋势,更多的关于BDNF与其前体(precursor of brain derived neurothrophic factor,proBDNF)以及BDNF与其它神经递质在神经网络中的相互作用的研究需要被深入开展. 相似文献
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V. I. Zemelko I. V. Kozhucharova Z. V. Kovaleva A. P. Domnina N. A. Pugovkina I. I. Fridlyanskaya M. V. Puzanov S. V. Anisimov T. M. Grinchuk N. N. Nikolsky 《Cell and Tissue Biology》2014,8(4):283-291
The ability of mesenchymal stem cells (MSCs) to differentiate into neuronal lineage determines the potential of these cells as a substrate for a cell replacement therapy. In this paper we compare the neurogenic potential of the MSCs from different donors, isolated from the bone marrow (BMSC), subcutaneous adipose tissue (AD MSC) and menstrual blood (eMSC). It was established that the native eMCSs, BMSCs and AD MSCs express neuronal marker β-III-tubulin with a frequency of 90, 50 and 14%, respectively. Also we showed that the eMSCs have a high endogenous level of brain-derived neurotrophic factor (BDNF), whereas the BMSCs and the AD MSCs are characterized by low basal BDNF levels. An induction of neuronal differentiation in the studied MSCs using differentiation medium containing B27 and N2 supplements, 5-azacytidine, retinoic acid, IBMX and dbcAMP induced changes in the cells morphology, the increase of β-III-tubulin expression, and the appearance of neuronal markers GFAP, NF-H, NeuN and MAP2. During the differentiation the BDNF secretion was significantly enhanced in the BMSCs and decreased in the eMSCs cultures. However, no correlation between the basal and induced levels of the neuronal markers expression in the studied MSCs has been established. 相似文献
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Numakawa T Richards M Adachi N Kishi S Kunugi H Hashido K 《Neurochemistry international》2011,59(5):551-558
MicroRNAs (miRs), endogenous small RNAs, regulate gene expression through repression of translational activity after binding to target mRNAs. miRs are involved in various cellular processes including differentiation, metabolism, and apoptosis. Furthermore, possible involvement of miRs in neuronal function have been proposed. For example, miR-132 is closely related to neuronal outgrowth while miR-134 plays a role in postsynaptic regulation, suggesting that brain-specific miRs are critical for synaptic plasticity. On the other hand, numerous studies indicate that BDNF (brain-derived neurotrophic factor), one of the neurotrophins, is essential for a variety of neuronal aspects such as cell differentiation, survival, and synaptic plasticity in the central nervous system (CNS). Interestingly, recent studies, including ours, suggest that BDNF exerts its beneficial effects on CNS neurons via up-regulation of miR-132. Here, we present a broad overview of the current knowledge concerning the association between neurotrophins and various miRs. 相似文献
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McAllister AK 《Neuron》2002,36(4):549-550
In this issue of Neuron, Zhang and Poo present evidence for localized BDNF-induced synaptic potentiation that is accompanied by spatially restricted calcium influx and requires local axonal protein synthesis. These results are consistent with a synapse-specific role for BDNF and provide a potentially novel way to think about cellular mechanisms for potentiation of neurotransmitter release. 相似文献
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Noble EE Billington CJ Kotz CM Wang C 《American journal of physiology. Regulatory, integrative and comparative physiology》2011,300(5):R1053-R1069
Brain-derived neurotrophic factor (BDNF) mediates energy metabolism and feeding behavior. As a neurotrophin, BDNF promotes neuronal differentiation, survival during early development, adult neurogenesis, and neural plasticity; thus, there is the potential that BDNF could modify circuits important to eating behavior and energy expenditure. The possibility that "faulty" circuits could be remodeled by BDNF is an exciting concept for new therapies for obesity and eating disorders. In the hypothalamus, BDNF and its receptor, tropomyosin-related kinase B (TrkB), are extensively expressed in areas associated with feeding and metabolism. Hypothalamic BDNF and TrkB appear to inhibit food intake and increase energy expenditure, leading to negative energy balance. In the hippocampus, the involvement of BDNF in neural plasticity and neurogenesis is important to learning and memory, but less is known about how BDNF participates in energy homeostasis. We review current research about BDNF in specific brain locations related to energy balance, environmental, and behavioral influences on BDNF expression and the possibility that BDNF may influence energy homeostasis via its role in neurogenesis and neural plasticity. 相似文献
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Nicola Kuczewski Christophe Porcher Volkmar Lessmann Igor Medina Jean-Luc Gaiarsa 《Molecular neurobiology》2009,39(1):37-49
Network construction and reorganization is modulated by the level and pattern of synaptic activity generated in the nervous
system. During the past decades, neurotrophins, and in particular brain-derived neurotrophic factor (BDNF), have emerged as
attractive candidates for linking synaptic activity and brain plasticity. Thus, neurotrophin expression and secretion are
under the control of activity-dependent mechanisms and, besides their classical role in supporting neuronal survival neurotrophins,
modulate nearly all key steps of network construction from neuronal migration to experience-dependent refinement of local
connections. In this paper, we provide an overview of recent findings showing that BDNF can serve as a target-derived messenger
for activity-dependent synaptic plasticity and development at the single cell level. 相似文献