Purinergic Signalling Mediates Aberrant Excitability of Developing Neuronal Circuits in the Fmr1 Knockout Mouse Model

Reynolds, Kathryn E.; Huang, Eileen; Sabbineni, Monica; Wiseman, Eliza; Murtaza, Nadeem; Ahuja, Desmond; Napier, Matt; Murphy, Kathryn M.; Singh, Karun K.; Scott, Angela L.

doi:10.1007/s12035-024-04181-w

Cited by 6Genetics and Neurodevelopmental DisordersAdenosine and Purinergic SignalingNeuroscience and Neuropharmacology Research

Purinergic Signalling Mediates Aberrant Excitability of Developing Neuronal Circuits in the Fmr1 Knockout Mouse Model

Reynolds, Kathryn E., Huang, Eileen, Sabbineni, Monica, Wiseman, Eliza, Murtaza, Nadeem, Ahuja, Desmond, Napier, Matt, Murphy, Kathryn M. +2 more·2024·Molecular Neurobiology

DOI 10.1007/s12035-024-04181-w

Open this paper in CoChat — free account

Abstract

Neuronal hyperexcitability within developing cortical circuits is a common characteristic of several heritable neurodevelopmental disorders, including Fragile X Syndrome (FXS), intellectual disability and autism spectrum disorders (ASD). While this aberrant circuitry is typically studied from a neuron-centric perspective, glial cells secrete soluble factors that regulate both neurite extension and synaptogenesis during development. The nucleotide-mediated purinergic signalling system is particularly instrumental in facilitating these effects. We recently reported that within a FXS animal model, the Fmr1 KO mouse, the purinergic signalling system is upregulated in cortical astrocytes leading to altered secretion of synaptogenic and plasticity-related proteins. In this study, we examined whether elevated astrocyte purinergic signalling also impacts neuronal morphology and connectivity of Fmr1 KO cortical neurons. Here, we found that conditioned media from primary Fmr1 KO astrocytes was sufficient to enhance neurite extension and complexity of both wildtype and Fmr1 KO neurons to a similar degree as UTP-mediated outgrowth. Significantly enhanced firing was also observed in Fmr1 KO neuron-astrocyte co-cultures grown on microelectrode arrays but was associated with large deficits in firing synchrony. The selective P2Y 2 purinergic receptor antagonist AR-C 118925XX effectively normalized much of the aberrant Fmr1 KO activity, designating P2Y 2 as a potential therapeutic target in FXS. These results not only demonstrate the importance of astrocyte soluble factors in the development of neural circuitry, but also show that P2Y purinergic receptors play a distinct role in pathological FXS neuronal activity.

Integrity signals

Registry

Crossref · 10.1007/s12035-024-04181-w

Cites

69 of 69 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome
Verkerk, A. J. M. H., Pieretti, M., Sutcliffe, J. S., Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Reiner, O., Richards, S., Victoria, M. F., Zhang, F., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90397-h · Cited by 3,481 · see citing works
Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox
Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Pieretti, M., Sutcliffe, J. S., Richards, S., Verkert, A. J. M. H., Holden, J. J. A., Fenwick, R. G., Warren, S. T., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90283-5 · Cited by 2,080 · see citing works
FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072 · see citing works
Absence of expression of the FMR-1 gene in fragile X syndrome
Pieretti, M., Zhang, F., Fu, Y.-H., Warren, S. T., Oostra, B. A., Caskey, C. T., & Nelson, D. L. (1991) · Cell · doi:10.1016/0092-8674(91)90125-i · Cited by 1,476 · see citing works
Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways
Chung, W.-S., Clarke, L. E., Wang, G. X., Stafford, B. K., Sher, A., Chakraborty, C., Joung, J., Foo, L. C., Thompson, A., Chen, C., et al. (2013) · Nature · doi:10.1038/nature12776 · Cited by 1,377 · see citing works
The art of using t-SNE for single-cell transcriptomics
Kobak, D., & Berens, P. (2019) · Nature Communications · doi:10.1038/s41467-019-13056-x · Cited by 1,118 · see citing works
Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome
Brown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., Jin, X., Feng, Y., Wilkinson, K. D., Keene, J. D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00568-2 · Cited by 1,109 · see citing works
Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis
Eroglu, Ç., Allen, N. J., Susman, M. W., O'Rourke, N. A., Park, C. Y., Özkan, E., Chakraborty, C., Mulinyawe, S. B., Annis, D. S., Huberman, A. D., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.025 · Cited by 893 · see citing works
Purinergic signalling in the nervous system: an overview
Abbracchio, M. P., Burnstock, G., Verkhratsky, A., & Zimmermann, H. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.10.001 · Cited by 856 · see citing works
How to use t-SNE effectively
Wattenberg, M., Viégas, F., & Johnson, I. (2016) · Distill · doi:10.23915/distill.00002 · Cited by 854 · see citing works
UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis
Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., Joshi, B. V., Jacobson, K. A., Kohsaka, S., & Inoue, K. (2007) · Nature · doi:10.1038/nature05704 · Cited by 802 · see citing works
DNA methylation represses <i>FMR-1</i> transcription in fragile X syndrome
Sutcliffe, J. S., Nelson, D. L., Zhang, F., Pieretti, M., Caskey, C. T., Saxe, D., & Warren, S. T. (1992) · Human Molecular Genetics · doi:10.1093/hmg/1.6.397 · Cited by 680 · 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
Astrocyte calcium waves: What they are and what they do
Scemes, E., & Giaume, C. (2006) · Glia · doi:10.1002/glia.20374 · Cited by 588 · see citing works
Imbalance of Neocortical Excitation and Inhibition and Altered UP States Reflect Network Hyperexcitability in the Mouse Model of Fragile X Syndrome
Gibson, J. R., Bartley, A. F., Hays, S. A., & Huber, K. M. (2008) · Journal of Neurophysiology · doi:10.1152/jn.90752.2008 · Cited by 529 · see citing works
Rescue of Fragile X Syndrome Neurons by DNA Methylation Editing of the FMR1 Gene
Liu, X. S., Wu, H., Krzisch, M., Wu, X., Graef, J. D., Muffat, J., Hnisz, D., Li, C. H., Yuan, B., Xu, C., et al. (2018) · Cell · doi:10.1016/j.cell.2018.01.012 · Cited by 506 · see citing works
From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome
Bagni, C., & Greenough, W. T. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1667 · Cited by 475 · see citing works
Underconnected, but How? A Survey of Functional Connectivity MRI Studies in Autism Spectrum Disorders
Müller, R., Shih, P., Keehn, B., Deyoe, J. R., Leyden, K. M., & Shukla, D. K. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhq296 · Cited by 450 · see citing works
Circuit level defects in the developing neocortex of fragile X mice
Gonçalves, J. T., Anstey, J. E., Golshani, P., & Portera-Cailliau, C. (2013) · Nature Neuroscience · doi:10.1038/nn.3415 · Cited by 279 · see citing works
Epilepsy and EEG Findings in Males with Fragile X Syndrome
Musumeci, S. A., Hagerman, R. J., Ferri, R., Bosco, P., Bernardina, B. D., Tassinari, C. A., Sarro, G. D., & Elia, M. (1999) · Epilepsia · doi:10.1111/j.1528-1157.1999.tb00824.x · Cited by 250 · see citing works
Localization of FMRP‐associated mRNA granules and requirement of microtubules for activity‐dependent trafficking in hippocampal neurons
Antar, L. N., Dictenberg, J. B., Plociniak, M., Afroz, R., & Bassell, G. J. (2005) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2005.00128.x · Cited by 246 · see citing works
Drosophila Fragile X Protein, DFXR, Regulates Neuronal Morphology and Function in the Brain
Morales, J., Hiesinger, P. R., Schroeder, A. J., Kume, K., Verstreken, P., Jackson, F. R., Nelson, D. L., & Hassan, B. A. (2002) · Neuron · doi:10.1016/s0896-6273(02)00731-6 · Cited by 238 · see citing works
Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1−/y mice
Zhang, Y., Bonnan, A., Bony, G., Férézou, I., Pietropaolo, S., Ginger, M. R., Sans, N., Rossier, J., Oostra, B. A., LeMasson, G., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3864 · Cited by 227 · see citing works
Decreased GABAA receptor expression in the seizure-prone fragile X mouse
Idrissi, A. E., Ding, X., Scalia, J., Trenkner, E., Brown, W. T., & Dobkin, C. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.11.087 · Cited by 210 · see citing works
Circuit and Plasticity Defects in the Developing Somatosensory Cortex of<i>Fmr1</i>Knock-Out Mice
Bureau, I., Shepherd, G. M. G., & Svoboda, K. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1076-08.2008 · Cited by 201 · see citing works
The Drosophila Fragile X Gene Negatively Regulates Neuronal Elaboration and Synaptic Differentiation
Pan, L., Zhang, Y., Woodruff, E. A., & Broadie, K. S. (2004) · Current Biology · doi:10.1016/j.cub.2004.09.085 · Cited by 194 · see citing works
Reduced habituation of auditory evoked potentials indicate cortical hyper-excitability in Fragile X Syndrome.
Ethridge, L. E., White, S. P., Mosconi, M. W., Wang, J., Byerly, M. J., & Sweeney, J. A. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.48 · Cited by 188 · see citing works
Astrocytes prevent abnormal neuronal development in the fragile X mouse.
Jacobs, S., & Doering, L. C. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5027-09.2010 · Cited by 170 · see citing works
In vivo cellular and molecular mechanisms of neuronal apoptosis in the mammalian CNS
Lossi, L., & Merighi, A. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(03)00051-0 · Cited by 169 · see citing works
Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome
Ethridge, L. E., White, S. P., Mosconi, M. W., Wang, J., Pedapati, E. V., Erickson, C. A., Byerly, M., & Sweeney, J. A. (2017) · Molecular Autism · doi:10.1186/s13229-017-0140-1 · Cited by 166 · see citing works
Local brain connectivity across development in autism spectrum disorder: A cross‐sectional investigation
Dajani, D. R., & Uddin, L. Q. (2015) · Autism Research · doi:10.1002/aur.1494 · Cited by 134 · see citing works
Increased Glutamate Concentration in the Auditory Cortex of Persons With Autism and First‐Degree Relatives: A 1H‐MRS Study
Brown, M. S., Singel, D., Hepburn, S., & Rojas, D. C. (2012) · Autism Research · doi:10.1002/aur.1260 · Cited by 133 · see citing works
Somatosensory cortical barrel dendritic abnormalities in a mouse model of the fragile X mental retardation syndrome
Galvez, R., Gopal, A. R., & Greenough, W. T. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02363-1 · Cited by 118 · see citing works
Hyperconnectivity and Slow Synapses during Early Development of Medial Prefrontal Cortex in a Mouse Model for Mental Retardation and Autism
Testa-Silva, G., Loebel, A., Giugliano, M., de Kock, C. P. J., Mansvelder, H. D., & Meredith, R. M. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhr224 · Cited by 118 · see citing works
Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial
Naviaux, R. K., Curtis, B., Li, K., Naviaux, J. C., Bright, A. T., Reiner, G., Westerfield, M., Goh, S., Alaynick, W. A., Wang, L., et al. (2017) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.424 · Cited by 112 · see citing works
Uridine enhances neurite outgrowth in nerve growth factor-differentiated pheochromocytoma cells
Pooler, A. M., Guez, D. H., Benedictus, R., & Wurtman, R. J. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.03.050 · Cited by 110 · see citing works
Impaired inhibitory control of cortical synchronization in fragile X syndrome
Paluszkiewicz, S. M., Olmos-Serrano, J. L., Corbin, J. G., & Huntsman, M. M. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00421.2011 · Cited by 107 · see citing works
Selective deletion of astroglial FMRP dysregulates glutamate transporter GLT1 and contributes to fragile X syndrome phenotypes in vivo.
Higashimori, H., Schin, C. S., Chiang, M. S. R., Morel, L., Shoneye, T. A., Nelson, D. L., & Yang, Y. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1069-16.2016 · Cited by 105 · see citing works
Calcium regulation of the brain-derived neurotrophic factor gene
Finkbeiner, S. M. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000701 · Cited by 102 · see citing works
Purinergic signaling induces thrombospondin-1 expression in astrocytes
Tran, M. D., & Neary, J. T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603146103 · Cited by 100 · see citing works
Dysregulation of fragile × mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of individuals with autism: a postmortem brain study
Fatemi, S. H., & Folsom, T. D. (2011) · Molecular Autism · doi:10.1186/2040-2392-2-6 · Cited by 84 · see citing works
Astrocyte-secreted thrombospondin-1 modulates synapse and spine defects in the fragile X mouse model.
Cheng, C., Lau, S. K. M., & Doering, L. C. (2016) · Molecular Brain · doi:10.1186/s13041-016-0256-9 · Cited by 84 · see citing works
Astrocytic Contributions to Synaptic and Learning Abnormalities in a Mouse Model of Fragile X Syndrome
Hodges, J., Yu, X., Gilmore, A., Bennett, H. C., Tjia, M., Perna, J., Chen, C.-C., Li, X., Lu, J., & Zuo, Y. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.08.036 · Cited by 80 · see citing works
Activation of ADF/cofilin mediates attractive growth cone turning toward nerve growth factor and netrin‐1
Marsick, B. M., Flynn, K. C., Santiago‐Medina, M., Bamburg, J. R., & Letourneau, P. C. (2010) · Developmental Neurobiology · doi:10.1002/dneu.20800 · Cited by 77 · see citing works
The inhibition of phosphatidylinositol‐3‐kinase induces neurite retraction and activates GSK3
Sanchez, S. P., Sayas, C. L., Lim, F., Díaz‐Nido, J., Ávila, J., & Wandosell, F. G. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00453.x · Cited by 75 · see citing works
Functional Deficiencies in Fragile X Neurons Derived from Human Embryonic Stem Cells
Telias, M., Kuznitsov-Yanovsky, L., Segal, M., & Ben‐Yosef, D. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0317-15.2015 · Cited by 68 · see citing works
The contribution of inhibitory interneurons to circuit dysfunction in Fragile X Syndrome
Rio, C. A. C.-D., & Huntsman, M. M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00245 · Cited by 67 · see citing works
Postsynaptic FMRP Promotes the Pruning of Cell-to-Cell Connections among Pyramidal Neurons in the L5A Neocortical Network
Patel, A. B., Loerwald, K. W., Huber, K. M., & Gibson, J. R. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2921-13.2014 · Cited by 67 · see citing works
Immunolocalization of P2Y4 and P2Y2 Purinergic Receptors in Strial Marginal Cells and Vestibular Dark Cells
Sage, C., & Marcus, D. C. (2002) · The Journal of Membrane Biology · doi:10.1007/s00232-001-0116-z · Cited by 65 · see citing works
Expression and function of the metabotropic purinergic P2Y receptor family in experimental seizure models and patients with drug‐refractory epilepsy
Alves, M., Gómez‐Villafuertes, R., Delanty, N., Farrell, M. A., O’Brien, D. F., Miras‐Portugal, M. T., Hernández, M. D., Henshall, D. C., & Engel, T. (2017) · Epilepsia · doi:10.1111/epi.13850 · Cited by 65 · see citing works
Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks
Kolen, K. V., & Slegers, H. (2006) · Purinergic Signalling · doi:10.1007/s11302-006-9008-0 · Cited by 64 · see citing works
Effect of GLT-1 modulator and P2X7 antagonists alone and in combination in the kindling model of epilepsy in rats
Soni, N., Koushal, P., Reddy, B. V. K., Deshmukh, R. R., & Kumar, P. (2015) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2015.04.056 · Cited by 57 · see citing works
RSKC: AnRPackage for a Robust and Sparse K-Means Clustering Algorithm
Kondo, Y., Salibián‐Barrera, M., & Zamar, R. H. (2016) · Journal of Statistical Software · doi:10.18637/jss.v072.i05 · Cited by 57 · see citing works
Comparative analysis of P2Y4 and P2Y6 receptor architecture in native and transfected neuronal systems
D’Ambrosi, N., Iafrate, M., Saba, E., Rosa, P., & Volonté, C. (2007) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2007.03.020 · Cited by 51 · see citing works
Down-regulation of striatin, a neuronal calmodulin-binding protein, impairs rat locomotor activity
Bartoli, M., Ternaux, J., Forni, C., Portalier, P., Salin, P., Amalric, M., & Monneron, A. (1999) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(199908)40:2 · Cited by 48 · see citing works
Regulation of IL-6 secretion by astrocytes via TLR4 in the fragile X mouse model.
Krasovska, V., & Doering, L. C. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00272 · Cited by 47 · see citing works
Partial FMRP expression is sufficient to normalize neuronal hyperactivity in Fragile X neurons
Graef, J. D., Wu, H., Ng, C., Sun, C., Villegas, V., Qadir, D., Jesseman, K., Warren, S. T., Jaenisch, R., Cacace, A. M., et al. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14660 · Cited by 42 · see citing works
Sensory hypo-excitability in a rat model of fetal development in Fragile X Syndrome
Berzhanskaya, J., Phillips, M. A., Shen, J., & Colonnese, M. T. (2016) · Scientific Reports · doi:10.1038/srep30769 · Cited by 41 · see citing works
Up‐regulation and activation of the P2Y2 nucleotide receptor mediate neurite extension in IL ‐1β‐treated mouse primary cortical neurons
Peterson, T. S., Thebeau, C. N., Ajit, D., Camden, J. M., Woods, L. T., Wood, W. G., Petris, M. J., Sun, G. Y., Erb, L., & Weisman, G. A. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12252 · Cited by 40 · see citing works
Regulation of axonal growth and guidance by the neurotrophin family of neurotrophic factors
Gillespie, L. N. (2003) · Clinical and Experimental Pharmacology and Physiology · doi:10.1046/j.1440-1681.2003.03909.x · Cited by 40 · see citing works
Altered developmental expression of the astrocyte-secreted factors hevin and SPARC in the fragile X mouse model.
Wallingford, J., Scott, A. L., Rodrigues, K., & Doering, L. C. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00268 · Cited by 38 · see citing works
Self-citation
Expression of Astrocyte-Related Receptors in Cortical Dysplasia With Intractable Epilepsy
Sukigara, S., Dai, H., Nabatame, S., Otsuki, T., Hanai, S., Honda, R., SAITO, T. K., Nakagawa, E., Kaido, T., Sato, N., et al. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000099 · Cited by 37 · see citing works
Astrocyte‐mediated purinergic signaling is upregulated in a mouse model of Fragile X syndrome
Reynolds, K. E., Wong, C. R., & Scott, A. L. M. (2021) · Glia · doi:10.1002/glia.23997 · Cited by 25 · see citing works
Self-citation
P2Y1 receptor mediated neuronal fibre outgrowth in organotypic brain slice co-cultures
Heine, C., Sygnecka, K., Scherf, N., Grohmann, M., Braesigk, A., & Franke, H. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.02.001 · Cited by 17 · see citing works
Primary Dissociated Astrocyte and Neuron Co-culture
Jacobs, S. A., & Doering, L. C. (2009) · Springer protocols handbooks/Springer protocols · doi:10.1007/978-1-60761-292-6_16 · Cited by 15 · see citing works
Converging purinergic and immune signaling pathways drive IL-6 secretion by Fragile X cortical astrocytes via STAT3
Reynolds, K. E., Krasovska, V., & Scott, A. L. M. (2021) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2021.577745 · Cited by 14 · see citing works
Self-citation
Single-Cell and Neuronal Network Alterations in an In Vitro Model of Fragile X Syndrome
Moskalyuk, A., Vijver, S. V. D., Verstraelen, P., Vos, W. H. D., Kooy, R. F., & Giugliano, M. (2019) · Cerebral Cortex · doi:10.1093/cercor/bhz068 · Cited by 12 · see citing works
A Practical Guide to Sparse k-Means Clustering for Studying Molecular Development of the Human Brain
Balsor, J. L., Arbabi, K., Singh, D., Kwan, R., Zaslavsky, J., Jeyanesan, E., & Murphy, K. M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.668293 · Cited by 11 · see citing works
Self-citation
Expression of globular form acetylcholinesterase is not altered in P2Y1R knock-out mouse brain
Cui, J. D., Xu, M. L., Liu, E. Y. L., Dong, T. T.-X., Lin, H., Tsim, K. W. K., & Bi, C. W. C. (2016) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2016.06.028 · Cited by 3 · see citing works

Flagged first, then by citations

Still being checked.

Astrocyte-mediated purinergic signalling in the Fragile X mouse cortex
Reynolds, K. (2021) · MacSphere (McMaster University) · doi:10.71548/21342
Self-citation
Astrocyte‐mediated purinergic signaling is upregulated in a mouse model of Fragile X syndrome
Reynolds, K. E., Wong, C. R., & Scott, A. L. M. (2021) · Glia · doi:10.1002/glia.23997 · Cited by 25 · see citing works
Self-citation
Dysregulated Purinergic Signalling in Fragile X Syndrome Cortical Astrocytes
Reynolds, K. E., Napier, M., Fei, F., Green, K. M. J., & Scott, A. L. M. (2024) · NeuroMolecular Medicine · doi:10.1007/s12017-024-08802-4 · Cited by 3 · see citing works
Self-citation
Dysregulated Purinergic Signalling in the Developing Fmr1-Knockout Mouse Hippocampus
Napier, M. S. (2026) · MacSphere (McMaster University) · doi:10.71548/25574
Self-citation
Aberrant astrocyte signalling during hippocampal development in the Fmr1-knockout mouse model
Napier, M., Monneypenny, A., MacDonald, J., & Scott, A. (2026) · Glial health research. · doi:10.1016/j.ghres.2026.100021
Self-citation

Authors: Reynolds, K. E., Huang, E., Sabbineni, M., Wiseman, E., Murtaza, N., Ahuja, D., Napier, M., Murphy, K. M., Singh, K. K., & Scott, A. L.
Affiliations: McMaster University (CA)
University Health Network (CA)
University of Guelph (CA)
Corresponding author: Scott, Angela L.
ORCID: Reynolds, Kathryn E.
Sabbineni, Monica
Murtaza, Nadeem
Murphy, Kathryn M.
Singh, Karun K.
Scott, Angela L.
Venue: Molecular Neurobiology
Publisher: Springer Science and Business Media LLC
Published: 2024-04-23
Volume: 61
Issue: 11
Pages: 9507-9528
ISSN: 0893-7648 (ISSN-L)
1559-1182
DOI: 10.1007/s12035-024-04181-w
OpenAlex: W4395043942
Semantic Scholar: 888fb38ce849728e904ba14cf88646163d550e81
Cited by: 6
References: 69
Citations by year: 2026: 4 · 2025: 1 · 2024: 1
FWCI: 1.59
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Molecular Neurobiology (publishedVersion)
PubMed (publishedVersion)
Funders: Scottish Rite Charitable Foundation of Canada (21107)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: purinergic signaling, Fmr1 knockout mice, fragile X syndrome, astrocytes, neuronal hyperexcitability, P2Y2 receptor, UTP, neurite outgrowth, astrocyte-neuron co-culture, cortical development, neurodevelopmental disorders
MeSH terms: Animals, Astrocytes, Cells, Cultured, Disease Models, Animal, Fragile X Syndrome, Mice, Inbred C57BL, Nerve Net, Neurons, Signal Transduction, Neurites, Culture Media, Conditioned, Mice, Knockout, Coculture Techniques, Mice, Fragile X Messenger Ribonucleoprotein 1

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

Purinergic Signalling Mediates Aberrant Excitability of Developing Neuronal Circuits in the Fmr1 Knockout Mouse Model

Abstract

Integrity signals

Claims the paper makes

Cites

Cited by

Related

Record

About these checks