Chemokine CX3CL1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity
Abstract
Excitotoxicity is a cell death caused by excessive exposure to glutamate (Glu), contributing to neuronal degeneration in many acute and chronic CNS diseases. We explored the role of fractalkine/CX3CL1 on survival of hippocampal neurons exposed to excitotoxic doses of Glu. We found that: CX3CL1 reduces excitotoxicity when co-applied with Glu, through the activation of the ERK1/2 and PI3K/Akt pathways, or administered up to 8 h after Glu insult; CX3CL1 reduces the Glu-activated whole-cell current through mechanisms dependent on intracellular Ca2+; CX3CL1 is released from hippocampal cells after excitotoxic insult, likely providing an endogenous protective mechanism against excitotoxic cell death.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The chemokine fractalkine (CX3CL1) and its cognate receptor, CX3CR1, play an important role in neuroinflammation via paracrine signaling between neurons and microglia.
“The chemokine fractalkine (CX3CL1) and its cognate receptor, CX3CR1, play an important role in neuroinflammation via paracrine signaling between neurons and microglia.[12][13][14]”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [12]
Cites
Expression of CX <sub>3</sub> CR1 chemokine receptors on neurons and their role in neuronal survival
Meucci, O., Fatatis, A., Simen, A. A., & Miller, R. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090017497 · Cited by 385 · see citing works
Hughes, P. M., Botham, M. S., Frentzel, S., Mir, A., & Perry, V. H. (2002) · Glia · doi:10.1002/glia.10037 · Cited by 252 · see citing works
Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury
Soriano, S. G., Amaravadi, L. S., Wang, Y. F., Zhou, H., Yu, G. X., Tonra, J. R., Fairchild-Huntress, V., Fang, Q., Dunmore, J. H., Huszar, D., et al. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00033-4 · Cited by 222 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neuronal ‘On’ and ‘Off’ signals control microglia
Biber, K., Neumann, H., Inoue, K., & Boddeke, H. W. G. M. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.08.007 · Cited by 787 · see citing works
Lee, S., Varvel, N. H., Konerth, M. E., Xu, G., Cardona, A. E., Ransohoff, R. M., & Lamb, B. T. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100265 · Cited by 539 · see citing works
Cho, S.-H., Sun, B., Zhou, Y., Kauppinen, T. M., Halabisky, B., Wes, P., Ransohoff, R. M., & Gan, L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.254268 · Cited by 268 · see citing works
Protracted downregulation of CX3CR1 on microglia of aged mice after lipopolysaccharide challenge
Wynne, A. M., Henry, C. J., Huang, Y., Cleland, A., & Godbout, J. P. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.05.011 · Cited by 224 · see citing works
Modulating neurotoxicity through CX3CL1/CX3CR1 signaling
Limatola, C., & Ransohoff, R. M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00229 · Cited by 210 · see citing works
Self-citationLyons, A., Lynch, A. M., Downer, E. J., Hanley, R., O’Sullivan, J. B., Smith, A., & Lynch, M. A. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06253.x · Cited by 202 · see citing works
Selective activation of microglia facilitates synaptic strength
Clark, A. K., Gruber-Schoffnegger, D., Drdla-Schutting, R., Gerhold, K. J., Malcangio, M., & Sandkühler, J. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2061-14.2015 · Cited by 171 · see citing works
Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice
Garofalo, S., D’Alessandro, G., Chece, G., Brau, F., Maggi, L., Rosa, A., Porzia, A., Mainiero, F., Esposito, V., Lauro, C., et al. (2015) · Nature Communications · doi:10.1038/ncomms7623 · Cited by 129 · see citing works
Self-citationFractalkine-Induced MFG-E8 Leads to Enhanced Apoptotic Cell Clearance by Macrophages
Miksa, M., Amin, D., Wu, R., Dong, W., Ravikumar, T. S., & Wang, P. (2007) · Molecular Medicine · doi:10.2119/2007-00019.miksa · Cited by 118 · see citing works
Lauro, C., Di Angelantonio, S., Cipriani, R., Sobrero, F., Antonilli, L., Brusadin, V., Ragozzino, D., & Limatola, C. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.11.7590 · Cited by 110 · see citing works
Self-citationTime-dependent effects of CX3CR1 in a mouse model of mild traumatic brain injury
Febinger, H. Y., Thomasy, H. E., Pavlova, M. N., Ringgold, K. M., Barf, P. R., George, A. M., Grillo, J. N., Bachstetter, A. D., Garcia, J. A., Cardona, A. E., et al. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0386-5 · Cited by 110 · see citing works
“CX3CL1 also protects against excitotoxicity through the activation of the ERK1/2 and PI3K/Akt pathways [7, 8].”
Roseti, C., Fucile, S., Lauro, C., Martinello, K., Bertollini, C., Esposito, V., Mascia, A., Catalano, M., Aronica, E., Limatola, C., et al. (2013) · Epilepsia · doi:10.1111/epi.12354 · Cited by 92 · see citing works
Self-citationPeripheral Chemokine Levels in Women with Recurrent Major Depression with Suicidal Ideation
Grassi-Oliveira, R., Brieztke, E., Teixeira, A., Pezzi, J. C., Zanini, M., Lopes, R. P., & Bauer, M. E. (2012) · Revista Brasileira de Psiquiatria · doi:10.1590/s1516-44462012000100013 · Cited by 91 · see citing works
Ischemia-induced Neuronal Cell Death Is Mediated by Chemokine Receptor CX3CR1
Wang, J., Gan, Y., Han, P., Yin, J., Liu, Q., Ghanian, S., Gao, F., Gong, G., & Tang, Z. (2018) · Scientific Reports · doi:10.1038/s41598-017-18774-0 · Cited by 58 · see citing works
Yeo, S.-I., Kim, J.-E., Ryu, H. J., Seo, C. H., Lee, B. C., Choi, I.-G., Kim, D.-S., & Kang, T.-C. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2011.03.005 · Cited by 55 · see citing works
Neuronal Cx3cr1 Deficiency Protects against Amyloid β-Induced Neurotoxicity
Dworzak, J., Renvoisé, B., Habchi, J., Yates, E. V., Combadière, C., Knowles, T. P., Dobson, C. M., Blackstone, C., Paulsen, O., & Murphy, P. M. (2015) · PLOS ONE · doi:10.1371/journal.pone.0127730 · Cited by 30 · see citing works
- Authors
- Limatola, C., Lauro, C., Catalano, M., Ciotti, M. T., Bertollini, C., Di Angelantonio, S., Ragozzino, D., & Eusebi, F.
- Affiliations
- Istituto Pasteur (IT)
- Institute of Neurobiology and Molecular Medicine (IT)
- Venue
- Journal of Neuroimmunology
- Publisher
- Elsevier BV
- Published
- 2005-09
- Volume
- 166
- Issue
- 1-2
- Pages
- 19-28
- ISSN
- 0165-5728 (ISSN-L)
- OpenAlex
- W2032618901
- Cited by
- 153
- References
- 3
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 10 · 2023: 4 · 2022: 6 · 2021: 10 · 2020: 1 · 2019: 5 · 2018: 8 · 2017: 7 · 2016: 7 · 2015: 11 · 2014: 12 · 2013: 9 · 2012: 7
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroimmunology (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- fractalkine, excitotoxicity, glutamate, hippocampal neurons, neuroprotection, ERK signaling, PI3K/Akt signaling, intracellular calcium, excitatory postsynaptic currents
- MeSH terms
- Animals, Cell Survival, Cells, Cultured, Drug Administration Schedule, Drug Combinations, Electric Conductivity, Hippocampus, Membrane Proteins, Neurons, Neurotoxins, Rats, Wistar, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Excitatory Amino Acid Agonists, Neuroprotective Agents, Glutamic Acid, Chemokines, CX3C, Rats, Chemokine CX3CL1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
