Metalloproteinase inhibition prevents inhibitory synapse reorganization and seizure genesis
Open accessAbstract
The integrity and stability of interneurons in a cortical network are essential for proper network function. Loss of interneuron synaptic stability and precise organization can lead to disruptions in the excitation/inhibition balance, a characteristic of epilepsy. This study aimed to identify alterations to the GABAergic interneuron network in the piriform cortex (PC: a cortical area believed to be involved in the development of seizures) after kindling-induced seizures. Immunohistochemistry was used to mark perineuronal nets (PNNs: structures in the extracellular matrix that provide synaptic stability and restrict reorganization of inhibitory interneurons) and interneuron nerve terminals in control and kindled tissues. We found that PNNs were significantly decreased around parvalbumin-positive interneurons after the induction of experimental epilepsy. Additionally, we found layer-specific increases in GABA release sites originating from calbindin, calretinin, and parvalbumin interneurons, implying that there is a re-wiring of the interneuronal network. This increase in release sites was matched by an increase in GABAergic post-synaptic densities. We hypothesized that the breakdown of the PNN could be due to the activity of matrix metalloproteinases (MMP) and that the prevention of PNN breakdown may reduce the rewiring of interneuronal circuits and suppress seizures. To test this hypothesis we employed doxycycline, a broad spectrum MMP inhibitor, to stabilize PNNs in kindled rats. We found that doxycycline prevented PNN breakdown, re-organization of the inhibitory innervation, and seizure genesis. Our observations indicate that PNN degradation may be necessary for the development of seizures by facilitating interneuron plasticity and increased GABAergic activity.
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?
Perineuronal nets (PNN) regulate synaptic plasticity and rewiring of the network of interneurons.
“Importantly, PNN regulate the synaptic plasticity (Kochlamazashvili et al., 2010) and rewiring the network (Pollock et al., 2014) of the interneurons (Wen et al., 2018).”
From Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis (2020) · cites this paper as Pollock et al., 2014
Metalloproteinase inhibitors prevented seizures and MMP-9 knockout mice were less susceptible to pentylenetetrazole-induced seizures.
“Moreover, metalloproteinase inhibitors prevented seizures51 and MMP-9 knockout mice were less susceptible to pentylenetetrazole-induced seizures52.”
From Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy (2018) · cites this paper as [51]
Cites
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959 · see citing works
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Modification of seizure activity by electrical stimulation: II. Motor seizure
Racine, R. J. (1972) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(72)90177-0 · Cited by 7,141 · see citing works
Neurotrophin 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
Neuronal Diversity and Temporal Dynamics: The Unity of Hippocampal Circuit Operations
Klausberger, T., & Somogyi, P. (2008) · Science · doi:10.1126/science.1149381 · Cited by 2,050 · see citing works
Reactivation of Ocular Dominance Plasticity in the Adult Visual Cortex
Pizzorusso, T., Medini, P., Berardi, N., Chierzi, S., Fawcett, J. W., & Maffei, L. (2002) · Science · doi:10.1126/science.1072699 · Cited by 1,679 · see citing works
NEUROTROPHINS AND SYNAPTIC PLASTICITY
McAllister, A. K., Katz, L. C., & Lo, D. C. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.295 · Cited by 1,337 · see citing works
Metalloproteinases in biology and pathology of the nervous system
Yong, W. V., Power, C., Forsyth, P., & Edwards, D. (2001) · Nature Reviews Neuroscience · doi:10.1038/35081571 · Cited by 1,094 · see citing works
On The Cellular and Network Bases of Epileptic Seizures
McCormick, D. A., & Contreras, D. (2001) · Annual Review of Physiology · doi:10.1146/annurev.physiol.63.1.815 · Cited by 1,006 · see citing works
Development of Epileptic Seizures through Brain Stimulation at Low Intensity
Goddard, G. V. (1967) · Nature · doi:10.1038/2141020a0 · Cited by 866 · see citing works
Kindling and status epilepticus models of epilepsy: rewiring the brain
Morimoto, K., Fahnestock, M. L., & Racine, R. J. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.03.009 · Cited by 840 · see citing works
Reduction of Lipofuscin-like Autofluorescence in Fluorescently Labeled Tissue
Schnell, S. A., Staines, W. A., & Wessendorf, M. W. (1999) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215549904700601 · Cited by 691 · see citing works
Cellular and molecular basis of epilepsy
McNamara, J. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-06-03413.1994 · Cited by 649 · see citing works
Mechanisms of epileptogenesis and potential treatment targets
Pitkänen, A., & Łukasiuk, K. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70310-0 · Cited by 614 · see citing works
McBain, C. J., & Fisahn, A. (2001) · Nature Reviews Neuroscience · doi:10.1038/35049047 · Cited by 581 · see citing works
Galtrey, C. M., & Fawcett, J. W. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.09.006 · Cited by 575 · see citing works
Extracellular matrix molecules and synaptic plasticity
Dityatev, A., & Schachner, M. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1115 · Cited by 564 · see citing works
Fuchs, E. C., Zivkovic, A. R., Cunningham, M. O., Middleton, S., LeBeau, F. E. N., Bannerman, D. M., Rozov, A., Whittington, M. A., Traub, R. D., Rawlins, J. N. P., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.031 · Cited by 532 · see citing works
Interneuron Diversity series: Inhibitory interneurons and network oscillations in vitro
Whittington, M. A., & Traub, R. D. (2003) · Trends in Neurosciences · doi:10.1016/j.tins.2003.09.016 · Cited by 497 · see citing works
Griffin, M. O., Fricovsky, E. S., Ceballos, G. M., & Villarreal, F. J. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00047.2010 · Cited by 414 · see citing works
Disinhibition of rat hippocampal pyramidal cells by GABAergic afferents from the septum.
Tóth, K., Freund, T. F., & Miles, R. (1997) · The Journal of Physiology · doi:10.1113/jphysiol.1997.sp022033 · Cited by 395 · see citing works
Szklarczyk, A., Lapinska, J., Rylski, M., McKay, R. D. G., & Kaczmarek, L. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00920.2002 · Cited by 392 · see citing works
Tyrosine Phosphorylation of Transmembrane Ligands for Eph Receptors
Brückner, K., Pasquale, E. B., & Klein, R. (1997) · Science · doi:10.1126/science.275.5306.1640 · Cited by 391 · see citing works
Perineuronal nets — a specialized form of extracellular matrix in the adult nervous system
Celio, M. R., & Blümcke, I. (1994) · Brain Research Reviews · doi:10.1016/0165-0173(94)90006-x · Cited by 386 · see citing works
The perineuronal net and the control of CNS plasticity
Wang, D., & Fawcett, J. (2012) · Cell and Tissue Research · doi:10.1007/s00441-012-1375-y · Cited by 373 · see citing works
Composition of Perineuronal Net Extracellular Matrix in Rat Brain
Deepa, S. S., Carulli, D., Galtrey, C., Rhodes, K., Fukuda, J., Mikami, T., Sugahara, K., & Fawcett, J. W. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600544200 · Cited by 367 · see citing works
Multiple facets of GABAergic neurons and synapses: multiple fates of GABA signalling in epilepsies
Cossart, R., Bernard, C., & Ben‐Ari, Y. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.11.011 · Cited by 340 · see citing works
Important role of matrix metalloproteinase 9 in epileptogenesis
Wilczynski, G. M., Konopacki, F. A., Wilczek, E., Lasiecka, Z., Gorlewicz, A., Michaluk, P., Wawrzyniak, M., Malinowska, M., Okulski, P., Kolodziej, L. R., et al. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200708213 · Cited by 292 · see citing works
Control of extracellular cleavage of ProBDNF by high frequency neuronal activity
Nagappan, G., Zaitsev, E. N., Senatorov, V. V., Yang, J., Hempstead, B. L., & Lu, B. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807322106 · Cited by 267 · see citing works
Dityatev, A. E., Seidenbecher, C. I., & Schachner, M. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2010.08.003 · Cited by 229 · see citing works
Kindling: some old and some new
McIntyre, D., Poulter, M. O., & Gilby, K. L. (2002) · Epilepsy Research · doi:10.1016/s0920-1211(02)00071-2 · Cited by 183 · see citing works
Self-citationZaremba, S., Guimaraes, A., Kalb, R. G., & Hockfield, S. J. (1989) · Neuron · doi:10.1016/0896-6273(89)90305-x · Cited by 182 · see citing works
Jourquin, J., Tremblay, E., Décanis, N., Charton, G., Hanessian, S., Chollet, A., Le Diguardher, T., Khrestchatisky, M., & Rivera, S. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02876.x · Cited by 178 · see citing works
The Brain’s Extracellular Matrix and Its Role in Synaptic Plasticity
Frischknecht, R., & Gundelfinger, E. D. (2012) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-7091-0932-8_7 · Cited by 156 · see citing works
The perineuronal net component of the extracellular matrix in plasticity and epilepsy
McRae, P. A., & Porter, B. E. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.08.007 · Cited by 143 · see citing works
Peng, Z., Zhang, N., Wei, W., Huang, C. S., Cetina, Y., Otis, T. S., & Houser, C. R. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2045-13.2013 · Cited by 114 · see citing works
Yuan, W., Matthews, R. T., Sandy, J. D., & Gottschall, P. E. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00347-0 · Cited by 109 · see citing works
Xu, B., Michalski, B., Racine, R. J., & Fahnestock, M. L. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.03.044 · Cited by 100 · see citing works
Persistent decrease in multiple components of the perineuronal net following status epilepticus
McRae, P. A., Baranov, E., Rogers, S. L., & Porter, B. E. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08268.x · Cited by 85 · see citing works
Adamec, R. E., & Stark-Adamec, C. I. (1983) · PubMed · Cited by 82 · see citing works
Amygdala lesions and CER learning: Long term effect of kindling
McIntyre, D., & Molino, A. (1972) · Physiology & Behavior · doi:10.1016/0031-9384(72)90197-7 · Cited by 71 · see citing works
Mizoguchi, H., Yamada, K., & Nabeshima, T. (2011) · Biochemistry Research International · doi:10.1155/2011/681385 · Cited by 68 · see citing works
Takács, E., Nyilas, R., Szepesi, Z., Baracskay, P., Karlsen, B., Røsvold, T., Bjørkum, A. A., Czurkó, A., Kovács, Z., Kékesi, A. K., et al. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.03.003 · Cited by 63 · see citing works
Kim, G. W., Kim, H.-J., Cho, K.-J., Kim, H.-W., Cho, Y.-J., & Lee, B. I. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.07.008 · Cited by 63 · see citing works
Organization of GABAA receptor α‐subunit clustering in the developing rat neocortex and hippocampus
Hutcheon, B., Fritschy, J., & Poulter, M. O. (2004) · European Journal of Neuroscience · doi:10.1111/j.0953-816x.2004.03349.x · Cited by 60 · see citing works
Self-citationMcIntyre, D., & Plant, J. (1993) · Brain Research · doi:10.1016/0006-8993(93)90086-3 · Cited by 52 · see citing works
McRae, P. A., Baranov, E., Sarode, S., Brooks-Kayal, A. R., & Porter, B. E. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.05.015 · Cited by 49 · see citing works
Electrical properties of neocortical neurons in slices from children with intractable epilepsy
Tasker, J. G., Hoffman, N. W., Kim, Y. I., Fisher, R. S., Peacock, W. J., & Dudek, F. E. (1996) · Journal of Neurophysiology · doi:10.1152/jn.1996.75.2.931 · Cited by 44 · see citing works
Sato, T., Yamada, N., Morimoto, K., Uemura, S., & Kuroda, S. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00895-6 · Cited by 41 · see citing works
Gavrilovici, C., Pollock, E., Everest, M. E., & Poulter, M. O. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.07.002 · Cited by 30 · see citing works
Self-citationDiverse interneuron populations have highly specific interconnectivity in the rat piriform cortex
Gavrilovici, C., D’Alfonso, S., & Poulter, M. O. (2009) · The Journal of Comparative Neurology · doi:10.1002/cne.22291 · Cited by 29 · see citing works
Self-citationNeural Growth, Neural Damage and Neurotrophins in the Kindling Model of Epilepsy
Racine, R. J., Adams, B., Osehobo, P., & Fahnestock, M. L. (2002) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-1335-3_16 · Cited by 19 · see citing works
McIntyre, D., & Poultert, M. O. (2001) · International review of neurobiology · doi:10.1016/s0074-7742(01)45020-3 · Cited by 18 · see citing works
Birjandian, Z., Narla, C., & Poulter, M. O. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2013.00183 · Cited by 12 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Neuron–glia interactions in the pathophysiology of epilepsy
Patel, D. C., Tewari, B. P., Chaunsali, L., & Sontheimer, H. W. (2019) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0126-4 · Cited by 461 · see citing works
Astrocytes in the initiation and progression of epilepsy
Vezzani, A., Ravizza, T., Bedner, P., Aronica, E., Steinhäuser, C., & Boison, D. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00727-5 · Cited by 272 · see citing works
Reinhard, S. M., Razak, K., & Ethell, I. M. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00280 · Cited by 219 · see citing works
Tewari, B. P., Chaunsali, L., Campbell, S. L., Patel, D. C., Goode, A. E., & Sontheimer, H. (2018) · Nature Communications · doi:10.1038/s41467-018-07113-0 · Cited by 208 · see citing works
Neuroinflammatory targets and treatments for epilepsy validated in experimental models
Aronica, E., Bauer, S., Bozzi, Y., Caleo, M., Dingledine, R. J., Gorter, J. A., Henshall, D. C., Kaufer, D., Koh, S., Löscher, W., et al. (2017) · Epilepsia · doi:10.1111/epi.13783 · Cited by 194 · see citing works
Self-citationThe Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders
Wen, T. H., Binder, D. K., Ethell, I. M., & Razak, K. A. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00270 · Cited by 170 · see citing works
Perineuronal Nets in the Adult Sensory Cortex Are Necessary for Fear Learning
Banerjee, S. B., Gutzeit, V. A., Baman, J., Aoued, H. S., Doshi, N. K., Liu, R. C., & Ressler, K. J. (2017) · Neuron · doi:10.1016/j.neuron.2017.06.007 · Cited by 163 · see citing works
Miyata, S., & Kitagawa, H. (2017) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2017.06.010 · Cited by 171 · see citing works
Perineuronal nets in brain physiology and disease
Testa, D., Prochiantz, A., & Nardo, A. A. D. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.09.011 · Cited by 141 · see citing works
The Piriform Cortex and Human Focal Epilepsy
Vaughan, D. N., & Jackson, G. D. (2014) · Frontiers in Neurology · doi:10.3389/fneur.2014.00259 · Cited by 143 · see citing works
Dwir, D., Giangreco, B., Xin, L., Tenenbaum, L., Cabungcal, J.-H., Steullet, P., Goupil, A., Cleusix, M., Jenni, R., Chtarto, A., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0393-5 · Cited by 137 · see citing works
Kim, S. Y., Senatorov, V. V., Morrissey, C. S., Lippmann, K., Vazquez, O. N., Milikovsky, D. Z., Gu, F., Parada, I., Prince, D. A., Becker, A. J., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-07394-3 · Cited by 136 · see citing works
Wiera, G., & Mozrzymas, J. W. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00427 · Cited by 117 · see citing works
In Sickness and in Health: Perineuronal Nets and Synaptic Plasticity in Psychiatric Disorders
Pantazopoulos, H., & Berretta, S. (2015) · Neural Plasticity · doi:10.1155/2016/9847696 · Cited by 118 · see citing works
Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy
Jiang, X., Lachance, M., & Rossignol, E. (2016) · Progress in brain research · doi:10.1016/bs.pbr.2016.04.012 · Cited by 98 · see citing works
Perineuronal net degradation in epilepsy
Rankin‐Gee, E. K., McRae, P. A., Baranov, E., Rogers, S., Wandrey, L., & Porter, B. E. (2015) · Epilepsia · doi:10.1111/epi.13026 · Cited by 100 · see citing works
Bozzelli, P. L., Alaiyed, S., Kim, E., Villapol, S., & Conant, K. E. (2018) · Neural Plasticity · doi:10.1155/2018/5735789 · Cited by 90 · see citing works
Releasing Addiction Memories Trapped in Perineuronal Nets
Lasek, A. W., Chen, H., & Chen, W.-Y. (2018) · Trends in Genetics · doi:10.1016/j.tig.2017.12.004 · Cited by 71 · see citing works
Gomez, S. T., Blonde, J. D., Mendoza-Halliday, D., Kuebler, E. S., Everest, M., Wang, X., Inoue, W., Poulter, M. O., & Martínez-Trujillo, J. (2020) · Cerebral Cortex · doi:10.1093/cercor/bhaa056 · Cited by 68 · see citing works
Self-citationNeurovascular unit dysfunction as a mechanism of seizures and epilepsy during aging
van Vliet, E. A., & Marchi, N. (2022) · Epilepsia · doi:10.1111/epi.17210 · Cited by 68 · see citing works
Increased metalloproteinase activity in the hippocampus following status epilepticus
Dubey, D., McRae, P. A., Rankin-Gee, E. K., Baranov, E., Wandrey, L., Rogers, S., & Porter, B. E. (2017) · Epilepsy Research · doi:10.1016/j.eplepsyres.2017.02.021 · Cited by 65 · see citing works
Stamenković, V., Stamenković, S., Jaworski, T., Gawlak, M., Jovanović, M., Jakovčevski, I., Wilczynski, G. M., Kaczmarek, L., Schachner, M., Radenović, L., et al. (2016) · Brain Structure and Function · doi:10.1007/s00429-016-1224-y · Cited by 60 · see citing works
Perineuronal Net Dynamics in the Pathophysiology of Epilepsy
Chaunsali, L., Tewari, B. P., & Sontheimer, H. W. (2021) · Epiliepsy currents/Epilepsy currents · doi:10.1177/15357597211018688 · Cited by 60 · see citing works
Korotkov, A., Broekaart, D. W. M., van Scheppingen, J., Anink, J. J., Baayen, J. C., Idema, S., Gorter, J. A., Aronica, E., & van Vliet, E. A. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1245-y · Cited by 60 · see citing works
Normal Development of the Perineuronal Net in Humans; In Patients with and without Epilepsy
Rogers, S. L., Rankin-Gee, E., Risbud, R. M., Porter, B. E., & Marsh, E. D. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.05.039 · Cited by 58 · see citing works
Luca, C. D., & Papa, M. (2016) · Neurochemical Research · doi:10.1007/s11064-016-1876-2 · Cited by 52 · see citing works
Disruption of perineuronal nets increases the frequency of sharp wave ripple events
Sun, Z. Y., Bozzelli, P. L., Caccavano, A., Allen, M., Balmuth, J., Vicini, S., Wu, J., & Conant, K. E. (2017) · Hippocampus · doi:10.1002/hipo.22804 · Cited by 55 · see citing works
Alaiyed, S., Bozzelli, P. L., Caccavano, A., Wu, J. Y., & Conant, K. E. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14671 · Cited by 52 · see citing works
Two matrix metalloproteinase classes reciprocally regulate synaptogenesis
Dear, M. L., Dani, N., Parkinson, W. M., Zhou, S., & Broadie, K. S. (2015) · Development · doi:10.1242/dev.124461 · Cited by 49 · see citing works
Bock, M. D., Wang, N., Decrock, E., Bultynck, G., & Leybaert, L. (2015) · Mediators of Inflammation · doi:10.1155/2015/257471 · Cited by 48 · see citing works
Extracellular matrix modulation is driven by experience-dependent plasticity during stroke recovery.
Quattromani, M. J., Pruvost, M., Guerreiro, C., Backlund, F., Englund, E., Aspberg, A., Jaworski, T., Hakon, J., Ruscher, K., Kaczmarek, L., et al. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0461-2 · Cited by 39 · see citing works
Redox and Immune Signaling in Schizophrenia: New Therapeutic Potential
Dwir, D., Khadimallah, I., Xin, L., Rahman, M., Du, F., Öngür, D., & Kim, Q. (2023) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyad012 · Cited by 40 · see citing works
Matrix Metalloproteinases, Neural Extracellular Matrix, and Central Nervous System Pathology
Luca, C. D., & Papa, M. (2017) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.04.002 · Cited by 39 · see citing works
Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory Synapses
Wiera, G., & Mozrzymas, J. W. (2021) · Cells · doi:10.3390/cells10082055 · Cited by 36 · see citing works
Impaired Cognitive Function after Perineuronal Net Degradation in the Medial Prefrontal Cortex
Paylor, J. W., Wendlandt, E., Freeman, T. S., Greba, Q., Marks, W. N., Howland, J. G., & Winship, I. R. (2018) · eNeuro · doi:10.1523/eneuro.0253-18.2018 · Cited by 37 · see citing works
Regulation of the E/I-balance by the neural matrisome
Mueller-Buehl, C., Wegrzyn, D., Bauch, J., & Faissner, A. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1102334 · Cited by 32 · see citing works
Vallés, A. S., & Barrantes, F. J. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.744597 · Cited by 33 · see citing works
The Role of Perineuronal Nets in Physiology and Disease: Insights from Recent Studies
Auer, S., Schicht, M., Hoffmann, L., Budday, S., Frischknecht, R., Blümcke, I., & Paulsen, F. P. (2025) · Cells · doi:10.3390/cells14050321 · Cited by 30 · see citing works
Tao, H., Gong, Y., Yu, Q., Zhou, H., & Liu, Y. (2020) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2019.0137 · Cited by 30 · see citing works
Serum metalloproteinase 9 levels increase after generalized tonic-clonic seizures
Cudna, A., Jopowicz, A., Mierzejewski, P., & Kurkowska‐Jastrzębska, I. (2016) · Epilepsy Research · doi:10.1016/j.eplepsyres.2016.11.006 · Cited by 29 · see citing works
Puścian, A., Winiarski, M., Łęski, S., Charzewski, Ł., Nikolaev, T., Borowska, J., Dzik, J. M., Bijata, M., Lipp, H., Dziembowska, M., et al. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15319 · Cited by 27 · see citing works
Susceptibility to hippocampal kindling seizures is increased in aging C57 black mice
Stover, K. R., Lim, S., Zhou, T.-L., Stafford, P. M., Chow, J., Li, H., Sivanenthiran, N., Mylvaganam, S. M., Wu, C., Weaver, D. F., et al. (2017) · IBRO Reports · doi:10.1016/j.ibror.2017.08.001 · Cited by 25 · see citing works
McKillop, W. M., York, E. M., Rubinger, L., Liu, T., Ossowski, N. M., Xu, K., Hryciw, T., & Brown, A. M. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.05.028 · Cited by 24 · see citing works
Self-citationStructural Changes Observed in the Piriform Cortex in a Rat Model of Pre-motor Parkinson’s Disease
Sancandi, M., Schul, E. V., Economides, G., Constanti, A., & Mercer, A. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00479 · Cited by 22 · see citing works
Takechi, K., Suemaru, K., Kiyoi, T., Tanaka, A., & Araki, H. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.02.021 · Cited by 21 · see citing works
Yang, P., Davidson, J. O., Fowke, T. M., Galinsky, R., Wassink, G., Karunasinghe, R. N., Prasad, J. D., Ranasinghe, S., Green, C. R., Bennet, L., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186475 · Cited by 17 · see citing works
Shilts, J., & Broadie, K. S. (2017) · Journal of Cell Science · doi:10.1242/jcs.200808 · Cited by 16 · see citing works
Woo, A. M., & Sontheimer, H. W. (2023) · Frontiers in Molecular Medicine · doi:10.3389/fmmed.2023.1198021 · Cited by 15 · see citing works
Modulatory Effects of Monoamines and Perineuronal Nets on Output of Cerebellar Purkinje Cells
Hirono, M., Karube, F., & Yanagawa, Y. (2021) · Frontiers in Neural Circuits · doi:10.3389/fncir.2021.661899 · Cited by 14 · see citing works
Altered Extracellular Matrix as an Alternative Risk Factor for Epileptogenicity in Brain Tumors
de Jong, J. M., Broekaart, D. W. M., Bongaarts, A., Mühlebner, A., Mills, J. D., van Vliet, E. A., & Aronica, E. (2022) · Biomedicines · doi:10.3390/biomedicines10102475 · Cited by 14 · see citing works
Perineuronal nets: Role in normal brain physiology and aging, and pathology of various diseases
Zhu, K., Fu, Y., Zhao, Y., Niu, B., & Han, L. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102756 · Cited by 16 · see citing works
Extracellular matrix: a new player in memory maintenance and psychiatric disorders
Bach, D. R., Brown, S. A., Kleim, B., & Tyagarajan, S. K. (2019) · Swiss Medical Weekly · doi:10.4414/smw.2019.20060 · Cited by 11 · see citing works
Ueno, H., Suemitsu, S., Murakami, S., Kitamura, N., Wani, K., Takahashi, Y., Matsumoto, Y., Okamoto, M., & Ishihara, T. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.07.019 · Cited by 11 · see citing works
Contribution of perineuronal nets to hyperexcitability in pilocarpine‐induced status epilepticus
Woo, A. M., Fleischel, E. J., Patel, D. C., & Sontheimer, H. W. (2025) · Epilepsia · doi:10.1111/epi.18489 · Cited by 8 · see citing works
Xiao, J., Huang, J., & Yolken, R. H. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100728 · Cited by 7 · see citing works
Yang, L. T., Anthony, G., & Kaufer, D. (2024) · doi:10.1093/med/9780197549469.003.0028 · Cited by 6 · see citing works
Perineuronal nets: Cruise from a honeycomb to the safety nets
John, U., Patro, N., & Patro, I. K. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.10.004 · Cited by 6 · see citing works
Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis
Al-Amin, M. M., Grandjean, J., Klohs, J., & Kim, J. (2020) · doi:10.1101/2020.04.27.064634 · Cited by 2 · see citing works
“Importantly, PNN regulate the synaptic plasticity (Kochlamazashvili et al., 2010) and rewiring the network (Pollock et al., 2014) of the interneurons (Wen et al., 2018).”
BackgroundNorman, A. O., Farooq, N., Sahni, A., Tapia, K., Breiner, D., Razak, K. A., & Ethell, I. M. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115184 · Cited by 2 · see citing works
Huang, Y.-F., Liu, C., Liu, Z., Zhuang, X., Chen, J.-H., Zhang, Z.-N., Shen, C., & Hu, Y. (2026) · Brain · doi:10.1093/brain/awag058 · Cited by 2 · see citing works
Трофимов, А. Н., Shcherbakova, K., Schwarz, A. P., Akbay, B., Karapina, O., Myrkhiyeva, Z., Shirokov, E., Kizatov, B., Zhukanov, K., Baktursyn, A., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27156606 · Cited by 3 · see citing works
Takechi, K. (2019) · YAKUGAKU ZASSHI · doi:10.1248/yakushi.19-00159 · Cited by 2 · see citing works
Séguin, D., KHAN, A. R., & Duerden, E. G. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2409-8_14 · Cited by 2 · see citing works
Dheer, A., Dixit, A. B., Tripathi, M., Chandra, P. S., & Banerjee, J. (2022) · Springer eBooks · doi:10.1007/978-981-16-8313-8_12 · Cited by 1 · see citing works
Gestational stress disrupts the neuroimmune environment in the nucleus accumbens of maternal rats
Dye, C. N., Franceschelli, D. V., Goodpaster, C. M., Wangler, L. M., Ringland, A., Godbout, J. P., Lenz, K. M., & Leuner, B. (2025) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2025.101140 · Cited by 1 · see citing works
Pathological Synaptic Plasticity in Neurological Disorders
Jin, C., & Karlstedt, K. (2025) · Synaptic Plasticity - Neurobiology, Neuroanatomy, and Clinical Neuroscience · doi:10.5772/intechopen.1007753 · Cited by 1 · see citing works
GABAergic Axosomatic Synapses of Rat Brain Cortex
Razenkova, V. A., & Korzhevsky, D. E. (2021) · Cell and Tissue Biology · doi:10.1134/s1990519x21030093 · Cited by 1 · see citing works
Paul, D., Srivastava, A., Banerjee, J., Tripathi, M., Doddamani, R. S., Lalwani, S., Siraj, F., Sharma, M. C., Chandra, P. S., & Dixit, A. B. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.22.550041 · Cited by 1 · see citing works
THE THEORY AND PRACTICE OF RELAY TYPE INSTRUMENTS BASED ON RADIOACTIVE ISOTOPES
Shumilovskii, N. N., Yanushkovskii, V. A., & Taksar, I. M. (1959) · OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information)
PERINEURONAL NETS IN HIPPOCAMPAL AREA CA2: REGULATION BY ACTIVITY AND DISEASE
Carstens, K. E. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/khgn-dw13
Microglia: Key Players in Perineuronal Net Dynamics
Garmendia-Berges, M., & Puerta, E. (2025) · IntechOpen eBooks · doi:10.5772/intechopen.1012413
Nashawi, H., Foltz, C. T., Oh, N., Santiago, E. A., Selm, D. R., Herman, J. P., & Ulrich‐Lai, Y. M. (2026) · Brain Structure and Function · doi:10.1007/s00429-026-03141-5
Harnessing Neurogenic Potential of Glial Cell Types as an Emerging Strategy for Treating Epilepsy
Chesnokova, E., Kotova, I., Reznikova, A., Balaban, P. M., & Bal, N. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27209147
Extracellular matrix and perineuronal nets in neural plasticity, memory, and epileptogenesis
Zhu, H., Li, Q., Li, Y., & Wang, W. (2026) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2026.1945520
- Authors
- Pollock, E., Everest, M., Brown, A., & Poulter, M. O.
- Affiliations
- Western University (CA)
- Corresponding author
- Poulter, Michael O.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 70
- Pages
- 21-31
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2038770782
- Cited by
- 75
- References
- 54
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 11 · 2016: 6 · 2015: 6 · 2014: 1
- FWCI
- 6.10
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- matrix metalloproteinases, perineuronal nets, GABAergic interneurons, kindling, epilepsy, piriform cortex, doxycycline, parvalbumin interneurons, calbindin, calretinin, synaptic plasticity, excitation-inhibition balance, seizure genesis
- MeSH terms
- Animals, Disease Models, Animal, Doxycycline, Extracellular Matrix, gamma-Aminobutyric Acid, Interneurons, Kindling, Neurologic, Male, Neural Inhibition, Neuronal Plasticity, Parvalbumins, Random Allocation, Seizures, Synapses, Rats, Sprague-Dawley, Matrix Metalloproteinases, Matrix Metalloproteinase Inhibitors, Calbindins, Calbindin 2
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
