Definition of a Bidirectional Activity-Dependent Pathway Involving BDNF and Narp
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One of the cardinal features of neural development and adult plasticity is the contribution of activity-dependent signaling pathways. However, the interrelationships between different activity-dependent genes are not well understood. The immediate early gene neuronal-activity-regulated pentraxin (NPTX2 or Narp) encodes a protein that has been associated with excitatory synaptogenesis, AMPA receptor aggregation, and the onset of critical periods. Here, we show that Narp is a direct transcriptional target of brain-derived neurotrophic factor (BDNF), another highly regulated activity-dependent gene involved in synaptic plasticity. Unexpectedly, Narp is bidirectionally regulated by BDNF. Acute BDNF withdrawal results in downregulation of Narp, whereas transcription of Narp is greatly enhanced by BDNF. Furthermore, our results show that BDNF directly regulates Narp to mediate glutamatergic transmission and mossy fiber plasticity. Hence, Narp serves as a significant epistatic target of BDNF to regulate synaptic plasticity during periods of dynamic activity.
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NPTX2 is released from the pre-synaptic terminal in response to neuronal activity, seizure, long-term potentiation, or BDNF.
“It is released from the pre-synaptic terminal in response to neuronal activity, seizure (O’Brien et al. 1999), long-term potentiation (LTP) (Tsui et al. 1996) or brain-derived neurotrophic factor (BDNF) (Mariga et al. 2015).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Mariga et al. 2015
BDNF-induced NPTX2 is required for glutamatergic synaptic transmission and long-term potentiation in mossy fibres in the dentate gyrus.
“BNDF-induced NPTX2 is required for glutamatergic synaptic transmission and LTP in mossy fibres in the dendate gyrus (Mariga et al. 2015; Wibrand et al. 2006).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Mariga et al. 2015
BDNF bidirectionally regulates NPTX2 expression at the transcriptional level, even in the absence of neuronal activity.
“BDNF bidirectionally regulates NPTX2 expression at the transcriptional level, even in the absence of neuronal activity (Fig. 3a-2).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Mariga et al. 2015
Reduced BDNF levels described in several neurodegenerative disorders could lead to diminished NPTX2 synthesis, as BDNF is one of the main regulators of NPTX2.
“The reduced BDNF levels described in several neurodegenerative disorders could lead to a diminished NPTX2 synthesis, as BNDF is one of the main regulators of NPTX2 (Lima Giacobbo et al. 2019; Mariga et al. 2015) (Fig. 3b-2).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Mariga et al. 2015
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Cites
Short-Term Synaptic Plasticity
Zucker, R. S., & Regehr, W. G. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.092501.114547 · Cited by 5,068 · see citing works
da Luz, A. C. D. D. S., Dias, G. P., Bevilaqua, M. C. D. N., Cocks, G. D., Gardino, P. F., Thuret, S., & Nardi, A. E. (2013) · Neuropsychobiology · doi:10.1159/000353269 · Cited by 4,012 · see citing works
Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00035-7 · Cited by 3,888 · see citing works
Trk Receptors: Roles in Neuronal Signal Transduction
Huang, E. J., & Reichardt, L. F. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161629 · Cited by 2,537 · see citing works
Neurotrophins and their receptors: A convergence point for many signalling pathways
Chao, M. V. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1078 · Cited by 2,298 · see citing works
Self-citationNeurotrophin regulation of neural circuit development and function
Park, H., & Poo, M.-M. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3379 · Cited by 2,060 · see citing works
Neurotrophins and Neuronal Plasticity
Thoenen, H. (1995) · Science · doi:10.1126/science.270.5236.593 · Cited by 1,927 · see citing works
Short-Term Synaptic Plasticity
Zucker, R. S. (1989) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.12.030189.000305 · Cited by 1,450 · see citing works
Long-Lasting Neurotrophin-Induced Enhancement of Synaptic Transmission in the Adult Hippocampus
Kang, H., & Schuman, E. M. (1995) · Science · doi:10.1126/science.7886457 · Cited by 1,354 · see citing works
Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior
Chen, Z.-Y., Jing, D., Bath, K. G., Ieraci, A., Khan, T., Siao, C.-J., Herrera, D. G., Toth, M., Yang, C., McEwen, B. S., et al. (2006) · Science · doi:10.1126/science.1129663 · Cited by 1,340 · see citing works
Patterson, S. L., Abel, T., Deuel, T. A. S., Martin, K. C., Rose, J. C., & Kandel, E. R. (1996) · Neuron · doi:10.1016/s0896-6273(00)80140-3 · Cited by 1,233 · see citing works
Lyford, G. L., Yamagata, K., Kaufmann, W. E., Barnes, C. A., Sanders, L. K., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Lanahan, A. A., & Worley, P. F. (1995) · Neuron · doi:10.1016/0896-6273(95)90299-6 · Cited by 1,212 · see citing works
Self-citationQian, Z., Gilbert, M. E., Colicos, M. A., Kandel, E. R., & Kuhl, D. (1993) · Nature · doi:10.1038/361453a0 · Cited by 869 · see citing works
Essential Role for TrkB Receptors in Hippocampus-Mediated Learning
Minichiello, L., Korte, M., Wolfer, D., Kühn, R., Unsicker, K., Cestari, V., Rossi-Arnaud, C., Lipp, H.-P., Bonhoeffer, T., & Klein, R. (1999) · Neuron · doi:10.1016/s0896-6273(00)80853-3 · Cited by 799 · see citing works
Ying, S.-W., Futter, M., Rosenblum, K., Webber, M. J., Hunt, S. P., Bliss, T. V. P., & Bramham, C. R. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-05-01532.2002 · Cited by 784 · see citing works
Comparison of Two Forms of Long-Term Potentiation in Single Hippocampal Neurons
Zalutsky, R. A., & Nicoll, R. A. (1990) · Science · doi:10.1126/science.2114039 · Cited by 759 · see citing works
Isackson, P. J., Huntsman, M. M., Murray, K. D., & Gall, C. M. (1991) · Neuron · doi:10.1016/0896-6273(91)90234-q · Cited by 711 · see citing works
Balancing Plasticity/Stability Across Brain Development
Takesian, A. E., & Hensch, T. K. (2013) · Progress in Brain Research · doi:10.1016/b978-0-444-63327-9.00001-1 · Cited by 667 · see citing works
The Growth Cone Cytoskeleton in Axon Outgrowth and GuidancePreprint
Dent, E. W., Gupton, S. L., & Gertler, F. B. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001800 · Cited by 651 · see citing works
Ernfors, P., Bengzon, J., Kokaia, Z., Persson, H., & Lindvall, O. (1991) · Neuron · doi:10.1016/0896-6273(91)90084-d · Cited by 628 · see citing works
Davis, S., Vanhoutte, P., Pagès, C., Caboche, J., & Laroche, S. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-12-04563.2000 · Cited by 621 · see citing works
A Genetic Variant BDNF Polymorphism Alters Extinction Learning in Both Mouse and Human
Soliman, F., Glatt, C. E., Bath, K. G., Levita, L., Jones, R. M., Pattwell, S. S., Jing, D., Tottenham, N., Amso, D., Somerville, L. H., et al. (2010) · Science · doi:10.1126/science.1181886 · Cited by 585 · see citing works
Synapsins as mediators of BDNF-enhanced neurotransmitter release
Jovanovic, J. N., Czernik, A. J., Fienberg, A. A., Greengard, P., & Sihra, T. S. (2000) · Nature Neuroscience · doi:10.1038/73888 · Cited by 566 · see citing works
Neuronal Activity-Regulated Gene Transcription in Synapse Development and Cognitive Function
West, A. E., & Greenberg, M. E. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005744 · Cited by 532 · see citing works
Mechanism of TrkB-Mediated Hippocampal Long-Term Potentiation
Minichiello, L., Calella, A. M., Medina, D. L., Bonhoeffer, T., Klein, R., & Korte, M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00942-x · Cited by 506 · see citing works
Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product narp.
O’Brien, R. J., Xu, D., Petralia, R. S., Steward, O., Huganir, R. L., & Worley, P. (1999) · Neuron · doi:10.1016/s0896-6273(00)80782-5 · Cited by 471 · see citing works
Self-citationSpiegel, I., Mardinly, A. R., Gabel, H. W., Bazinet, J. E., Couch, C. H., Tzeng, C. P., Harmin, D. A., & Greenberg, M. E. (2014) · Cell · doi:10.1016/j.cell.2014.03.058 · Cited by 416 · cited 1× · see citing works
“There are hints that Narp and BDNF expression are related from microarray analyses of different environmental and developmental states (Tong et al., 2001; Wibrand et al., 2006; Spiegel et al., 2014).”
BDNF mechanisms in late LTP formation: A synthesis and breakdown
Panja, D., & Bramham, C. R. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.06.024 · Cited by 336 · see citing works
Patterson, S. L., Pittenger, C., Morozov, A., Martin, K. C., Scanlin, H., Drake, C., & Kandel, E. R. (2001) · Neuron · doi:10.1016/s0896-6273(01)00443-3 · Cited by 334 · see citing works
Effects of Exercise on Gene-Expression Profile in the Rat Hippocampus
Tong, L., Shen, H., Perreau, V. M., Balázs, R., & Cotman, C. W. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0427 · Cited by 325 · see citing works
Li, Y., Zhang, Y., Lester, H. A., Schuman, E. M., & Davidson, N. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-24-10231.1998 · Cited by 318 · see citing works
Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons
Chang, M. C., Park, J. M., Pelkey, K. A., Grabenstatter, H. L., Xu, D., Linden, D. J., Sutula, T. P., McBain, C. J., & Worley, P. F. (2010) · Nature Neuroscience · doi:10.1038/nn.2621 · Cited by 316 · see citing works
Self-citationTsui, C., Copeland, N., Gilbert, D., Jenkins, N., Barnes, C., & Worley, P. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-08-02463.1996 · Cited by 315 · see citing works
Self-citationCastillo, P. E., Weisskopf, M. G., & Nicoll, R. A. (1994) · Neuron · doi:10.1016/0896-6273(94)90269-0 · Cited by 298 · see citing works
Zinc-Mediated Transactivation of TrkB Potentiates the Hippocampal Mossy Fiber-CA3 Pyramid Synapse
Huang, Y. Z., Pan, E., Xiong, Z., & McNamara, J. O. (2008) · Neuron · doi:10.1016/j.neuron.2007.11.026 · Cited by 275 · see citing works
Xu, D., Hopf, C., Reddy, R., Cho, R. W., Guo, L., Lanahan, A., Petralia, R. S., Wenthold, R. J., O'Brien, R. J., & Worley, P. (2003) · Neuron · doi:10.1016/s0896-6273(03)00463-x · Cited by 265 · see citing works
Self-citationPelkey, K. A., Barksdale, E., Craig, M. T., Yuan, X., Sukumaran, M., Vargish, G. A., Mitchell, R. M., Wyeth, M. S., Petralia, R. S., Chittajallu, R., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.02.020 · Cited by 245 · see citing works
Self-citationCremer, H., Chazal, G., Carleton, A., Goridis, C., Vincent, J., & Lledo, P. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.13242 · Cited by 215 · see citing works
Binder, D. K., Routbort, M. J., & McNamara, J. O. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-11-04616.1999 · Cited by 188 · see citing works
Pan, E., Zhang, X., Huang, Z., Krężel, A., Zhao, M., Tinberg, C. E., Lippard, S. J., & McNamara, J. O. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.019 · Cited by 187 · see citing works
O'Brien, R., Xu, D., Mi, R., Tang, X., Hopf, C., & Worley, P. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-11-04487.2002 · Cited by 160 · see citing works
Self-citationWibrand, K., Messaoudi, E., Håvik, B., Steenslid, V., Løvlie, R., Steen, V. M., & Bramham, C. R. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04687.x · Cited by 153 · see citing works
Quantal analysis of paired-pulse facilitation in guinea pig hippocampal slices
Hess, G., Kuhnt, U., & Voronin, L. L. (1987) · Neuroscience Letters · doi:10.1016/0304-3940(87)90584-2 · Cited by 123 · see citing works
Purcell, A. L., Sharma, S. K., Bagnall, M. W., Sutton, M. A., & Carew, T. J. (2003) · Neuron · doi:10.1016/s0896-6273(03)00030-8 · Cited by 119 · see citing works
Obligatory Role for the Immediate Early Gene NARP in Critical Period Plasticity
Gu, Y., Huang, S., Chang, M., Worley, P. F., Kirkwood, A., & Quinlan, E. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.05.016 · Cited by 117 · see citing works
Self-citationSchildt, S., Endres, T., Leßmann, V., & Edelmann, E. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.03.041 · Cited by 55 · see citing works
Withdrawal of BDNF from hippocampal cultures leads to changes in genes involved in synaptic function
Mariga, A., Zavadil, J., Ginsberg, S. D., & Chao, M. V. (2014) · Developmental Neurobiology · doi:10.1002/dneu.22216 · Cited by 43 · see citing works
Self-citationProminent Narp expression in projection pathways and terminal fields
Reti, I. M., Reddy, R., Worley, P. F., & Baraban, J. M. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01051.x · Cited by 42 · see citing works
Self-citationWijayatunge, R., Chen, L., Cha, Y. M., Zannas, A. S., Frank, C. L., & West, A. E. (2014) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2014.06.008 · Cited by 36 · see citing works
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- He XP Minichiello L Klein R McNamara JO 2002 Immunochemical evidence of seizure-induced activation of trkB receptor in the mossy fiber pathway of mouse hippocampus J Neurosci 22 7502 7508 12196573 PMC6757988
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Mitre, M., Mariga, A., & Chao, M. V. (2017) · Clinical Science · doi:10.1042/cs20160044 · Cited by 263 · see citing works
Self-citationGómez de San José, N., Massa, F., Halbgebauer, S., Oeckl, P., Steinacker, P., & Otto, M. (2022) · Journal of Neural Transmission · doi:10.1007/s00702-021-02411-2 · Cited by 112 · see citing works
Boiten, W., van Steenoven, I., Xiao, M.-F., Worley, P., Noli, B., Cocco, C., Ferri, G.-L., Lemstra, A., & Teunissen, C. (2020) · Cells · doi:10.3390/cells10010038 · Cited by 42 · see citing works
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- Authors
- Mariga, A., Glaser, J., Mathias, L., Xu, D., Xiao, M., Worley, P., Ninan, I., & Chao, M. V.
- Affiliations
- NYU Langone Health (US)
- Génétique et biologie du développement (FR)
- Université Paris Diderot (FR)
- Johns Hopkins University (US)
- Corresponding author
- Chao, Moses V.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 13
- Issue
- 9
- Pages
- 1747-1756
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4681298
- OpenAlex
- W2208481176
- Cited by
- 45
- References
- 49
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 3
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institute on Aging (AG025870, P50AG005146, R01AG025970)
- National Institute of Mental Health (P50MH100024)
- National Institute of Neurological Disorders and Stroke (R01NS021072, NS-21072, R56NS021072)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD076914, HD076914)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- brain-derived neurotrophic factor, NARP, NPTX2, activity-dependent gene regulation, immediate early genes, synaptic plasticity, glutamatergic neurotransmission, critical period, hippocampus
- MeSH terms
- Pentraxins, Animals, C-Reactive Protein, Cells, Cultured, Dactinomycin, Female, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Promoter Regions, Genetic, Synapses, Signal Transduction, Transcriptional Activation, Down-Regulation, Rats, Sprague-Dawley, Receptors, AMPA, Brain-Derived Neurotrophic Factor, Mitogen-Activated Protein Kinases, Protein Kinase Inhibitors, Mice, Rats, Phospholipase C gamma
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