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Volume 32, Issue 9
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Perineuronal nets (PNN) is condensed extracellular matrix (ECM) in the central nervous system (CNS), which surrounds cell soma, axon initial segments, and synapses. In the brain, most neurons surrounded by PNN are interneurons, especially the parvalbumin-expressing interneurons (PVI). The formation of PNN is involved in the PVI maturation as well as the onset and closure of critical periods for developmental plasticity end. Dysfunction of PVI can lead to some neurological disorders, such as schizophrenia, bipolar depression, and Alzheimer's disease. Similarly, PNN assembling abnormalities are often observed in human patients and animal disease models. PNN is thought to have a neuroprotective effect and interact with signaling molecules to regulate synaptic plasticity and neuronal activity. In this review, we provide an overview of the composition, structure, and functions of PNN. In addition, we highlight abnormal changes in PNN components in pathological conditions. Understanding the roles of different components of PNN will bring us a new perspective on brain plasticity and neurological disorders.

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2023-11-08
2025-06-17

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References

  1. CelioM.R. SpreaficoR. De BiasiS. Vitellaro-ZuccarelloL. Perineuronal nets: Past and present.Trends Neurosci.1998211251051510.1016/S0166‑2236(98)01298‑39881847
     [Google Scholar]
  2. DityatevA. SchachnerM. Extracellular matrix molecules and synaptic plasticity.Nat. Rev. Neurosci.20034645646810.1038/nrn111512778118
     [Google Scholar]
  3. CarulliD. PizzorussoT. KwokJ.C.F. PutignanoE. PoliA. ForostyakS. AndrewsM.R. DeepaS.S. GlantT.T. FawcettJ.W. Animals lacking link protein have attenuated perineuronal nets and persistent plasticity.Brain201013382331234710.1093/brain/awq14520566484
     [Google Scholar]
  4. FawcettJ.W. OohashiT. PizzorussoT. The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function.Nat. Rev. Neurosci.201920845146510.1038/s41583‑019‑0196‑331263252
     [Google Scholar]
  5. BlosaM. SonntagM. BrücknerG. JägerC. SeegerG. MatthewsR.T. RübsamenR. ArendtT. MorawskiM. Unique features of extracellular matrix in the mouse medial nucleus of trapezoid body: Implications for physiological functions.Neuroscience201322821523410.1016/j.neuroscience.2012.10.00323069754
     [Google Scholar]
  6. VoT. CarulliD. EhlertE.M.E. KwokJ.C.F. DickG. MecollariV. MoloneyE.B. NeufeldG. de WinterF. FawcettJ.W. VerhaagenJ. The chemorepulsive axon guidance protein semaphorin3A is a constituent of perineuronal nets in the adult rodent brain.Mol. Cell. Neurosci.20135618620010.1016/j.mcn.2013.04.00923665579
     [Google Scholar]
  7. PizzorussoT. MediniP. BerardiN. ChierziS. FawcettJ.W. MaffeiL. Reactivation of ocular dominance plasticity in the adult visual cortex.Science200229855961248125110.1126/science.107269912424383
     [Google Scholar]
  8. BarrittA.W. DaviesM. MarchandF. HartleyR. GristJ. YipP. McMahonS.B. BradburyE.J. Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury.J. Neurosci.20062642108561086710.1523/JNEUROSCI.2980‑06.200617050723
     [Google Scholar]
  9. MasseyJ.M. HubscherC.H. WagonerM.R. DeckerJ.A. AmpsJ. SilverJ. OniferS.M. Chondroitinase ABC digestion of the perineuronal net promotes functional collateral sprouting in the cuneate nucleus after cervical spinal cord injury.J. Neurosci.200626164406441410.1523/JNEUROSCI.5467‑05.200616624960
     [Google Scholar]
  10. CarstensK.E. PhillipsM.L. Pozzo-MillerL. WeinbergR.J. DudekS.M. Perineuronal nets suppress plasticity of excitatory synapses on CA2 pyramidal neurons.J. Neurosci.201636236312632010.1523/JNEUROSCI.0245‑16.201627277807
     [Google Scholar]
  11. FrischknechtR. HeineM. PerraisD. SeidenbecherC.I. ChoquetD. GundelfingerE.D. Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity.Nat. Neurosci.200912789790410.1038/nn.233819483686
     [Google Scholar]
  12. LensjøK.K. LepperødM.E. DickG. HaftingT. FyhnM. Removal of perineuronal nets unlocks juvenile plasticity through network mechanisms of decreased inhibition and increased gamma activity.J. Neurosci.20173751269128310.1523/JNEUROSCI.2504‑16.201628039374
     [Google Scholar]
  13. MorelliniF. SivukhinaE. StoenicaL. OulianovaE. BukaloO. JakovcevskiI. DityatevA. IrintchevA. SchachnerM. Improved reversal learning and working memory and enhanced reactivity to novelty in mice with enhanced GABAergic innervation in the dentate gyrus.Cereb. Cortex201020112712272710.1093/cercor/bhq01720194688
     [Google Scholar]
  14. HappelM.F.K. NiekischH. Castiblanco RiveraL.L. OhlF.W. DelianoM. FrischknechtR. Enhanced cognitive flexibility in reversal learning induced by removal of the extracellular matrix in auditory cortex.Proc. Natl. Acad. Sci.201411172800280510.1073/pnas.131027211124550310
     [Google Scholar]
  15. BanerjeeS.B. GutzeitV.A. BamanJ. AouedH.S. DoshiN.K. LiuR.C. ResslerK.J. Perineuronal nets in the adult sensory cortex are necessary for fear learning.Neuron2017951169179.e310.1016/j.neuron.2017.06.00728648500
     [Google Scholar]
  16. GaltreyC.M. KwokJ.C.F. CarulliD. RhodesK.E. FawcettJ.W. Distribution and synthesis of extracellular matrix proteoglycans, hyaluronan, link proteins and tenascin-R in the rat spinal cord.Eur. J. Neurosci.20082761373139010.1111/j.1460‑9568.2008.06108.x18364019
     [Google Scholar]
  17. GiamancoK.A. MatthewsR.T. Deconstructing the perineuronal net: Cellular contributions and molecular composition of the neuronal extracellular matrix.Neuroscience201221836738410.1016/j.neuroscience.2012.05.05522659016
     [Google Scholar]
  18. AfshariF.T. KwokJ.C. WhiteL. FawcettJ.W. Schwann cell migration is integrin-dependent and inhibited by astrocyte-produced aggrecan.Glia2010587NA10.1002/glia.2097020155822
     [Google Scholar]
  19. AbaskharounM. BellemareM. LauE. MargolisR.U. Expression of hyaluronan and the hyaluronan-binding proteoglycans neurocan, aggrecan, and versican by neural stem cells and neural cells derived from embryonic stem cells.Brain Res.2010132761510.1016/j.brainres.2010.02.04820176001
     [Google Scholar]
  20. AsherR.A. MorgensternD.A. ShearerM.C. AdcockK.H. PeshevaP. FawcettJ.W. Versican is upregulated in CNS injury and is a product of oligodendrocyte lineage cells.J. Neurosci.20022262225223610.1523/JNEUROSCI.22‑06‑02225.200211896162
     [Google Scholar]
  21. LevyC. BrooksJ.M. ChenJ. SuJ. FoxM.A. Cell-specific and developmental expression of lectican-cleaving proteases in mouse hippocampus and neocortex.J. Comp. Neurol.2015523462964810.1002/cne.2370125349050
     [Google Scholar]
  22. BeurdeleyM. SpatazzaJ. LeeH.H.C. SugiyamaS. BernardC. Di NardoA.A. HenschT.K. ProchiantzA. Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex.J. Neurosci.201232279429943710.1523/JNEUROSCI.0394‑12.201222764251
     [Google Scholar]
  23. SugiyamaS. Di NardoA.A. AizawaS. MatsuoI. VolovitchM. ProchiantzA. HenschT.K. Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity.Cell2008134350852010.1016/j.cell.2008.05.05418692473
     [Google Scholar]
  24. FoscarinS. Raha-ChowdhuryR. FawcettJ.W. KwokJ.C.F. Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory.Aging2017961607162210.18632/aging.10125628657900
     [Google Scholar]
  25. BrücknerG. GroscheJ. SchmidtS. HärtigW. MargolisR.U. DelpechB. SeidenbecherC.I. CzanieraR. SchachnerM. Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R.J. Comp. Neurol.2000428461662910.1002/1096‑9861(20001225)428:4<616::AID‑CNE3>3.0.CO;2‑K11077416
     [Google Scholar]
  26. WeigelP.H. Hyaluronan synthase: The mechanism of initiation at the reducing end and a pendulum model for polysaccharide translocation to the cell exterior.Int. J. Cell Biol.2015201511510.1155/2015/36757926472958
     [Google Scholar]
  27. SasisekharanR. VenkataramanG. Heparin and heparan sulfate: Biosynthesis, structure and function.Curr. Opin. Chem. Biol.20004662663110.1016/S1367‑5931(00)00145‑911102866
     [Google Scholar]
  28. SugaharaK. KitagawaH. Heparin and heparan sulfate biosynthesis.IUBMB Life200254416317510.1080/1521654021492812512855
     [Google Scholar]
  29. YoshiokaN. MiyataS. TamadaA. WatanabeY. KawasakiA. KitagawaH. TakaoK. MiyakawaT. TakeuchiK. IgarashiM. Abnormalities in perineuronal nets and behavior in mice lacking CSGalNAcT1, a key enzyme in chondroitin sulfate synthesis.Mol. Brain20171014710.1186/s13041‑017‑0328‑528982363
     [Google Scholar]
  30. KwokJ.C.F. WarrenP. FawcettJ.W. Chondroitin sulfate: A key molecule in the brain matrix.Int. J. Biochem. Cell Biol.201244458258610.1016/j.biocel.2012.01.00422265655
     [Google Scholar]
  31. MatthewsR.T. KellyG.M. ZerilloC.A. GrayG. TiemeyerM. HockfieldS. Aggrecan glycoforms contribute to the molecular heterogeneity of perineuronal nets.J. Neurosci.200222177536754710.1523/JNEUROSCI.22‑17‑07536.200212196577
     [Google Scholar]
  32. McRaeP.A. RoccoM.M. KellyG. BrumbergJ.C. MatthewsR.T. Sensory deprivation alters aggrecan and perineuronal net expression in the mouse barrel cortex.J. Neurosci.200727205405541310.1523/JNEUROSCI.5425‑06.200717507562
     [Google Scholar]
  33. BrakebuschC. SeidenbecherC.I. AsztelyF. RauchU. MatthiesH. MeyerH. KrugM. BöckersT.M. ZhouX. KreutzM.R. MontagD. GundelfingerE.D. FässlerR. Brevican-deficient mice display impaired hippocampal CA1 long-term potentiation but show no obvious deficits in learning and memory.Mol. Cell. Biol.200222217417742710.1128/MCB.22.21.7417‑7427.200212370289
     [Google Scholar]
  34. Dours-ZimmermannM.T. MaurerK. RauchU. StoffelW. FässlerR. ZimmermannD.R. Versican V2 assembles the extracellular matrix surrounding the nodes of ranvier in the CNS.J. Neurosci.200929247731774210.1523/JNEUROSCI.4158‑08.200919535585
     [Google Scholar]
  35. ZhouX.H. BrakebuschC. MatthiesH. OohashiT. HirschE. MoserM. KrugM. SeidenbecherC.I. BoeckersT.M. RauchU. BuettnerR. GundelfingerE.D. FässlerR. Neurocan is dispensable for brain development.Mol. Cell. Biol.200121175970597810.1128/MCB.21.17.5970‑5978.200111486035
     [Google Scholar]
  36. MorawskiM. BrücknerG. ArendtT. MatthewsR.T. Aggrecan: Beyond cartilage and into the brain.Int. J. Biochem. Cell Biol.201244569069310.1016/j.biocel.2012.01.01022297263
     [Google Scholar]
  37. UenoH. FujiiK. SuemitsuS. MurakamiS. KitamuraN. WaniK. AokiS. OkamotoM. IshiharaT. TakaoK. Expression of aggrecan components in perineuronal nets in the mouse cerebral cortex.IBRO Rep.20184223710.1016/j.ibror.2018.01.00230135949
     [Google Scholar]
  38. McRaeP.A. BaranovE. SarodeS. Brooks-KayalA.R. PorterB.E. Aggrecan expression, a component of the inhibitory interneuron perineuronal net, is altered following an early-life seizure.Neurobiol. Dis.201039343944810.1016/j.nbd.2010.05.01520493259
     [Google Scholar]
  39. GiamancoK.A. MorawskiM. MatthewsR.T. Perineuronal net formation and structure in aggrecan knockout mice.Neuroscience201017041314132710.1016/j.neuroscience.2010.08.03220732394
     [Google Scholar]
  40. RowlandsD. LensjøK.K. DinhT. YangS. AndrewsM.R. HaftingT. FyhnM. FawcettJ.W. DickG. Aggrecan directs extracellular matrix-mediated neuronal plasticity.J. Neurosci.20183847101021011310.1523/JNEUROSCI.1122‑18.201830282728
     [Google Scholar]
  41. YuZ. ChenN. HuD. ChenW. YuanY. MengS. ZhangW. LuL. HanY. ShiJ. Decreased density of perineuronal net in prelimbic cortex is linked to depressive-like behavior in young-aged rats.Front. Mol. Neurosci.202013410.3389/fnmol.2020.0000432116542
     [Google Scholar]
  42. PantazopoulosH. MarkotaM. JaquetF. GhoshD. WallinA. SantosA. CatersonB. BerrettaS. Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: A postmortem study on the amygdala.Transl. Psychiatry201551e496e49610.1038/tp.2014.12825603412
     [Google Scholar]
  43. JakovljevićA. TucićM. BlažikováM. KorenićA. MissirlisY. StamenkovićV. AndjusP. Structural and functional modulation of perineuronal nets: In search of important players with highlight on tenascins.Cells2021106134510.3390/cells1006134534072323
     [Google Scholar]
  44. CelioM.R. Chiquet-EhrismannR. ‘Perineuronal nets’ around cortical interneurons expressing parvalbumin are rich in tenascin.Neurosci. Lett.19931621-213714010.1016/0304‑3940(93)90579‑A7510052
     [Google Scholar]
  45. Chiquet-EhrismannR. TuckerR.P. Tenascins and the importance of adhesion modulation.Cold Spring Harb. Perspect. Biol.201135a00496010.1101/cshperspect.a00496021441591
     [Google Scholar]
  46. MorawskiM. DityatevA. Hartlage-RübsamenM. BlosaM. HolzerM. FlachK. PavlicaS. DityatevaG. GroscheJ. BrücknerG. SchachnerM. Tenascin-R promotes assembly of the extracellular matrix of perineuronal nets via clustering of aggrecan.Philos. Trans. R. Soc. Lond. B Biol. Sci.201436916542014004610.1098/rstb.2014.004625225104
     [Google Scholar]
  47. SaghatelyanA.K. DityatevA. SchmidtS. SchusterT. BartschU. SchachnerM. Reduced perisomatic inhibition, increased excitatory transmission, and impaired long-term potentiation in mice deficient for the extracellular matrix glycoprotein tenascin-R.Mol. Cell. Neurosci.200117122624010.1006/mcne.2000.092211161481
     [Google Scholar]
  48. NikonenkoA. SchmidtS. SkiboG. BrücknerG. SchachnerM. Tenascin-R-deficient mice show structural alterations of symmetric perisomatic synapses in the CA1 region of the hippocampus.J. Comp. Neurol.2003456433834910.1002/cne.1053712532406
     [Google Scholar]
  49. GottschlingC. WegrzynD. DeneckeB. FaissnerA. Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses.Sci. Rep.2019911393910.1038/s41598‑019‑50404‑931558805
     [Google Scholar]
  50. DankovichT.M. KaushikR. OlsthoornL.H.M. PetersenG.C. GiroP.E. KlueverV. Agüi-GonzalezP. GreweK. BaoG. BeuermannS. HadiH.A. DoerenJ. KlöppnerS. CooperB.H. DityatevA. RizzoliS.O. Extracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R.Nat. Commun.2021121712910.1038/s41467‑021‑27462‑734880248
     [Google Scholar]
  51. OohashiT EdamatsuM BekkuY CarulliD The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity.Experim. Neurol.2015274Pt B134144
     [Google Scholar]
  52. BekkuY. SuW.D. HirakawaS. FässlerR. OhtsukaA. KangJ.S. SandersJ. MurakamiT. NinomiyaY. OohashiT. Molecular cloning of Bral2, a novel brain-specific link protein, and immunohistochemical colocalization with brevican in perineuronal nets.Mol. Cell. Neurosci.200324114815910.1016/S1044‑7431(03)00133‑714550776
     [Google Scholar]
  53. CarulliD. RhodesK.E. BrownD.J. BonnertT.P. PollackS.J. OliverK. StrataP. FawcettJ.W. Composition of perineuronal nets in the adult rat cerebellum and the cellular origin of their components.J. Comp. Neurol.2006494455957710.1002/cne.2082216374793
     [Google Scholar]
  54. RauchU. HirakawaS. OohashiT. KapplerJ. RoosG. Cartilage link protein interacts with neurocan, which shows hyaluronan binding characteristics different from CD44 and TSG-6.Matrix Biol.200422862963910.1016/j.matbio.2003.11.00715062856
     [Google Scholar]
  55. KwokJ.C.F. CarulliD. FawcettJ.W. In vitro modeling of perineuronal nets: Hyaluronan synthase and link protein are necessary for their formation and integrity.J. Neurochem.20101145no10.1111/j.1471‑4159.2010.06878.x20584105
     [Google Scholar]
  56. BekkuY. SaitoM. MoserM. FuchigamiM. MaeharaA. NakayamaM. KusachiS. NinomiyaY. OohashiT. Bral2 is indispensable for the proper localization of brevican and the structural integrity of the perineuronal net in the brainstem and cerebellum.J. Comp. Neurol.201252081721173610.1002/cne.2300922121037
     [Google Scholar]
  57. YangP. DavidsonJ.O. FowkeT.M. GalinskyR. WassinkG. KarunasingheR.N. PrasadJ.D. RanasingheS. GreenC.R. BennetL. GunnA.J. DeanJ.M. Connexin hemichannel mimetic peptide attenuates cortical interneuron loss and perineuronal net disruption following cerebral ischemia in near-term fetal sheep.Int. J. Mol. Sci.20202118647510.3390/ijms2118647532899855
     [Google Scholar]
  58. FowkeT.M. GalinskyR. DavidsonJ.O. WassinkG. KarunasingheR.N. PrasadJ.D. BennetL. GunnA.J. DeanJ.M. Loss of interneurons and disruption of perineuronal nets in the cerebral cortex following hypoxia-ischaemia in near-term fetal sheep.Sci. Rep.2018811768610.1038/s41598‑018‑36083‑y30523273
     [Google Scholar]
  59. PaulA. UlfigN. Lectin staining in the basal nucleus (Meynert) and the hypothalamic tuberomamillary nucleus of the developing human prosencephalon.Anat. Rec.1998252114915910.1002/(SICI)1097‑0185(199809)252:1<149::AID‑AR13>3.0.CO;2‑O9737751
     [Google Scholar]
  60. GaoR. WangM. LinJ. HuL. LiZ. ChenC. YuanL. Spatiotemporal expression patterns of chondroitin sulfate proteoglycan mRNAs in the developing rat brain.Neuroreport201829751752310.1097/WNR.000000000000095729271834
     [Google Scholar]
  61. MiyataS. KomatsuY. YoshimuraY. TayaC. KitagawaH. Persistent cortical plasticity by upregulation of chondroitin 6-sulfation.Nat. Neurosci.201215341442210.1038/nn.302322246436
     [Google Scholar]
  62. MuraseS. LantzC.L. QuinlanE.M. Light reintroduction after dark exposure reactivates plasticity in adults via perisynaptic activation of MMP-9.eLife20176e2734510.7554/eLife.2734528875930
     [Google Scholar]
  63. FoscarinS. PonchioneD. PajajE. LetoK. GawlakM. WilczynskiG.M. RossiF. CarulliD. Experience-dependent plasticity and modulation of growth regulatory molecules at central synapses.PLoS One201161e1666610.1371/journal.pone.001666621304956
     [Google Scholar]
  64. YuanW. MatthewsR.T. SandyJ.D. GottschallP.E. Association between protease-specific proteolytic cleavage of brevican and synaptic loss in the dentate gyrus of kainate-treated rats.Neuroscience200211441091110110.1016/S0306‑4522(02)00347‑012379262
     [Google Scholar]
  65. HuH. GanJ. JonasP. Fast-spiking, parvalbumin+ GABAergic interneurons: From cellular design to microcircuit function.Science20143456196125526310.1126/science.125526325082707
     [Google Scholar]
  66. BartosM. VidaI. JonasP. Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks.Nat. Rev. Neurosci.200781455610.1038/nrn204417180162
     [Google Scholar]
  67. SohalV.S. ZhangF. YizharO. DeisserothK. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance.Nature2009459724769870210.1038/nature0799119396159
     [Google Scholar]
  68. RehR.K. DiasB.G. NelsonC.A.III KauferD. WerkerJ.F. KolbB. LevineJ.D. HenschT.K. Critical period regulation across multiple timescales.Proc. Natl. Acad. Sci.202011738232422325110.1073/pnas.182083611732503914
     [Google Scholar]
  69. GundelfingerE.D. FrischknechtR. ChoquetD. HeineM. Converting juvenile into adult plasticity: A role for the brain’s extracellular matrix.Eur. J. Neurosci.201031122156216510.1111/j.1460‑9568.2010.07253.x20497467
     [Google Scholar]
  70. YeQ. MiaoQ. Experience-dependent development of perineuronal nets and chondroitin sulfate proteoglycan receptors in mouse visual cortex.Matrix Biol.201332635236310.1016/j.matbio.2013.04.00123597636
     [Google Scholar]
  71. LendvaiB. SternE.A. ChenB. SvobodaK. Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo. Nature2000404678087688110.1038/3500910710786794
     [Google Scholar]
  72. SternE.A. MaravallM. SvobodaK. Rapid development and plasticity of layer 2/3 maps in rat barrel cortex in vivo. Neuron200131230531510.1016/S0896‑6273(01)00360‑911502260
     [Google Scholar]
  73. HouX. YoshiokaN. TsukanoH. SakaiA. MiyataS. WatanabeY. YanagawaY. SakimuraK. TakeuchiK. KitagawaH. HenschT.K. ShibukiK. IgarashiM. SugiyamaS. Chondroitin sulfate is required for onset and offset of critical period plasticity in visual cortex.Sci. Rep.2017711264610.1038/s41598‑017‑04007‑x28974755
     [Google Scholar]
  74. RombergC. YangS. MelaniR. AndrewsM.R. HornerA.E. SpillantiniM.G. BusseyT.J. FawcettJ.W. PizzorussoT. SaksidaL.M. Depletion of perineuronal nets enhances recognition memory and long-term depression in the perirhinal cortex.J. Neurosci.201333167057706510.1523/JNEUROSCI.6267‑11.201323595763
     [Google Scholar]
  75. RowlandsD. LensjøK.K. DinhT. YangS. AndrewsM.R. HaftingT. FyhnM. FawcettJ.W. DickG. Aggrecan directs extracellular matrix-mediated neuronal plasticity.J. Neurosci.20183847101021011310.1523/JNEUROSCI.1122‑18.201830282728
     [Google Scholar]
  76. BrücknerG. GroscheJ. SchmidtS. HärtigW. MargolisR.U. DelpechB. SeidenbecherC.I. CzanieraR. SchachnerM. Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R.J. Comp. Neurol.2000428461662910.1002/1096‑9861(20001225)428:4<616::AID‑CNE3>3.0.CO;2‑K11077416
     [Google Scholar]
  77. ChangM.C. ParkJ.M. PelkeyK.A. GrabenstatterH.L. XuD. LindenD.J. SutulaT.P. McBainC.J. WorleyP.F. Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons.Nat. Neurosci.20101391090109710.1038/nn.262120729843
     [Google Scholar]
  78. GuY. HuangS. ChangM.C. WorleyP. KirkwoodA. QuinlanE.M. Obligatory role for the immediate early gene NARP in critical period plasticity.Neuron201379233534610.1016/j.neuron.2013.05.01623889936
     [Google Scholar]
  79. CarulliD. FoscarinS. FaralliA. PajajE. RossiF. Modulation of semaphorin3A in perineuronal nets during structural plasticity in the adult cerebellum.Mol. Cell. Neurosci.201357102210.1016/j.mcn.2013.08.00323999154
     [Google Scholar]
  80. SaghatelyanA. SnapyanM. GorissenS. MeigelI. MosbacherJ. KaupmannK. BettlerB. KornilovA.V. NifantievN.E. SakanyanV. SchachnerM. DityatevA. Recognition molecule associated carbohydrate inhibits postsynaptic GABAB receptors: A mechanism for homeostatic regulation of GABA release in perisomatic synapses.Mol. Cell. Neurosci.200324227128210.1016/S1044‑7431(03)00163‑514572452
     [Google Scholar]
  81. BukaloO. SchachnerM. DityatevA. Hippocampal metaplasticity induced by deficiency in the extracellular matrix glycoprotein tenascin-R.J. Neurosci.200727226019602810.1523/JNEUROSCI.1022‑07.200717537973
     [Google Scholar]
  82. DonatoF. RompaniS.B. CaroniP. Parvalbumin-expressing basket-cell network plasticity induced by experience regulates adult learning.Nature2013504747927227610.1038/nature1286624336286
     [Google Scholar]
  83. FavuzziE. Marques-SmithA. DeograciasR. WinterfloodC.M. Sánchez-AguileraA. MantoanL. MaesoP. FernandesC. EwersH. RicoB. Activity-dependent gating of parvalbumin interneuron function by the perineuronal net protein brevican.Neuron2017953639655.e1010.1016/j.neuron.2017.06.02828712654
     [Google Scholar]
  84. FavuzziE. RicoB. Molecular diversity underlying cortical excitatory and inhibitory synapse development.Curr. Opin. Neurobiol.20185381510.1016/j.conb.2018.03.01129704699
     [Google Scholar]
  85. KochlamazashviliG. HennebergerC. BukaloO. DvoretskovaE. SenkovO. LievensP.M.J. WestenbroekR. EngelA.K. CatterallW.A. RusakovD.A. SchachnerM. DityatevA. The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca(2+) channels.Neuron201067111612810.1016/j.neuron.2010.05.03020624596
     [Google Scholar]
  86. ThiagarajanT.C. LindskogM. TsienR.W. Adaptation to synaptic inactivity in hippocampal neurons.Neuron200547572573710.1016/j.neuron.2005.06.03716129401
     [Google Scholar]
  87. ShiW. WeiX. WangX. DuS. LiuW. SongJ. WangY. Perineuronal nets protect long-term memory by limiting activity-dependent inhibition from parvalbumin interneurons.Proc. Natl. Acad. Sci.201911652270632707310.1073/pnas.190268011631843906
     [Google Scholar]
  88. HironoM. WatanabeS. KarubeF. FujiyamaF. KawaharaS. NagaoS. YanagawaY. MisonouH. Perineuronal nets in the deep cerebellar nuclei regulate GABAergic transmission and delay eyeblink conditioning.J. Neurosci.201838276130614410.1523/JNEUROSCI.3238‑17.201829858484
     [Google Scholar]
  89. EdamatsuM. MiyanoR. FujikawaA. FujiiF. HoriT. SakabaT. OohashiT. Hapln4/Bral2 is a selective regulator for formation and transmission of GABAergic synapses between Purkinje and deep cerebellar nuclei neurons.J. Neurochem.2018147674876310.1111/jnc.1457130125937
     [Google Scholar]
  90. GriffithsS. ScottH. GloverC. BienemannA. GhorbelM.T. UneyJ. BrownM.W. WarburtonE.C. BashirZ.I. Expression of long-term depression underlies visual recognition memory.Neuron200858218619410.1016/j.neuron.2008.02.02218439404
     [Google Scholar]
  91. CarstensK.E. PhillipsM.L. Pozzo-MillerL. WeinbergR.J. DudekS.M. Perineuronal nets suppress plasticity of excitatory synapses on CA2 pyramidal neurons.J. Neurosci.201636236312632010.1523/JNEUROSCI.0245‑16.201627277807
     [Google Scholar]
  92. HayaniH. SongI. DityatevA. Increased excitability and reduced excitatory synaptic input into fast-spiking CA2 interneurons after enzymatic attenuation of extracellular matrix.Front. Cell. Neurosci.20181214910.3389/fncel.2018.0014929899690
     [Google Scholar]
  93. CopeE.C. ZychA.D. KatchurN.J. WatersR.C. LahamB.J. DiethornE.J. Atypical perineuronal nets in the CA2 region interfere with social memory in a mouse model of social dysfunction.Mol. Psychiatry20212783520353134183768
     [Google Scholar]
  94. RombergC. YangS. MelaniR. AndrewsM.R. HornerA.E. SpillantiniM.G. BusseyT.J. FawcettJ.W. PizzorussoT. SaksidaL.M. Depletion of perineuronal nets enhances recognition memory and long-term depression in the perirhinal cortex.J. Neurosci.201333167057706510.1523/JNEUROSCI.6267‑11.201323595763
     [Google Scholar]
  95. ShiW. WeiX. WangX. DuS. LiuW. SongJ. WangY. Perineuronal nets protect long-term memory by limiting activity-dependent inhibition from parvalbumin interneurons.Proc. Natl. Acad. Sci.201911652270632707310.1073/pnas.190268011631843906
     [Google Scholar]
  96. SlakerM. ChurchillL. ToddR.P. BlacktopJ.M. ZuloagaD.G. RaberJ. DarlingR.A. BrownT.E. SorgB.A. Removal of perineuronal nets in the medial prefrontal cortex impairs the acquisition and reconsolidation of a cocaine-induced conditioned place preference memory.J. Neurosci.201535104190420210.1523/JNEUROSCI.3592‑14.201525762666
     [Google Scholar]
  97. ThompsonE.H. LensjøK.K. WigestrandM.B. Malthe-SørenssenA. HaftingT. FyhnM. Removal of perineuronal nets disrupts recall of a remote fear memory.Proc. Natl. Acad. Sci.2018115360761210.1073/pnas.171353011529279411
     [Google Scholar]
  98. GogollaN. CaroniP. LüthiA. HerryC. Perineuronal nets protect fear memories from erasure.Science200932559451258126110.1126/science.117414619729657
     [Google Scholar]
  99. BanerjeeS.B. GutzeitV.A. BamanJ. AouedH.S. DoshiN.K. LiuR.C. ResslerK.J. Perineuronal nets in the adult sensory cortex are necessary for fear learning.Neuron2017951169179.e310.1016/j.neuron.2017.06.00728648500
     [Google Scholar]
  100. HylinM.J. OrsiS.A. MooreA.N. DashP.K. Disruption of the perineuronal net in the hippocampus or medial prefrontal cortex impairs fear conditioning.Learn. Mem.201320526727310.1101/lm.030197.11223592037
     [Google Scholar]
  101. ShenY. TenneyA.P. BuschS.A. HornK.P. CuascutF.X. LiuK. HeZ. SilverJ. FlanaganJ.G. PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration.Science2009326595259259610.1126/science.117831019833921
     [Google Scholar]
  102. EillG.J. SinhaA. MorawskiM. ViapianoM.S. MatthewsR.T. The protein tyrosine phosphatase RPTPζ/phosphacan is critical for perineuronal net structure.J. Biol. Chem.2020295495596810.1016/S0021‑9258(17)49907‑831822561
     [Google Scholar]
  103. LesnikovaA. CasarottoP. MolinerR. FredS.M. BiojoneC. CastrénE. Perineuronal net receptor PTPσ regulates retention of memories.Front. Synaptic Neurosci.20211367247510.3389/fnsyn.2021.67247534366821
     [Google Scholar]
  104. OhtakeY. SaitoA. LiS. Diverse functions of protein tyrosine phosphatase σ in the nervous and immune systems.Exp. Neurol.201830219620410.1016/j.expneurol.2018.01.01429374568
     [Google Scholar]
  105. TakahashiH. CraigA.M. Protein tyrosine phosphatases PTPδ, PTPσ, and LAR: Presynaptic hubs for synapse organization.Trends Neurosci.201336952253410.1016/j.tins.2013.06.00223835198
     [Google Scholar]
  106. LiW. KeiferJ. Coordinate action of pre- and postsynaptic brain-derived neurotrophic factor is required for AMPAR trafficking and acquisition of in vitro classical conditioning.Neuroscience2008155368669710.1016/j.neuroscience.2008.06.04318639615
     [Google Scholar]
  107. MorelliniF. SivukhinaE. StoenicaL. OulianovaE. BukaloO. JakovcevskiI. DityatevA. IrintchevA. SchachnerM. Improved reversal learning and working memory and enhanced reactivity to novelty in mice with enhanced GABAergic innervation in the dentate gyrus.Cereb. Cortex201020112712272710.1093/cercor/bhq01720194688
     [Google Scholar]
  108. KarunakaranS. ChowdhuryA. DonatoF. QuairiauxC. MichelC.M. CaroniP. PV plasticity sustained through D1/5 dopamine signaling required for long-term memory consolidation.Nat. Neurosci.201619345446410.1038/nn.423126807952
     [Google Scholar]
  109. HijaziS. HeistekT.S. ScheltensP. NeumannU. ShimshekD.R. MansvelderH.D. SmitA.B. van KesterenR.E. Early restoration of parvalbumin interneuron activity prevents memory loss and network hyperexcitability in a mouse model of Alzheimer’s disease.Mol. Psychiatry202025123380339810.1038/s41380‑019‑0483‑431431685
     [Google Scholar]
  110. GiamancoK.A. MorawskiM. MatthewsR.T. Perineuronal net formation and structure in aggrecan knockout mice.Neuroscience201017041314132710.1016/j.neuroscience.2010.08.03220732394
     [Google Scholar]
  111. ChristensenA.C. LensjøK.K. LepperødM.E. DraglyS.A. SutterudH. BlackstadJ.S. FyhnM. HaftingT. Perineuronal nets stabilize the grid cell network.Nat. Commun.202112125310.1038/s41467‑020‑20241‑w33431847
     [Google Scholar]
  112. CoueyJ.J. WitoelarA. ZhangS.J. ZhengK. YeJ. DunnB. CzajkowskiR. MoserM.B. MoserE.I. RoudiY. WitterM.P. Recurrent inhibitory circuitry as a mechanism for grid formation.Nat. Neurosci.201316331832410.1038/nn.331023334580
     [Google Scholar]
  113. KwokJ.C.F. CarulliD. FawcettJ.W. In vitro modeling of perineuronal nets: hyaluronan synthase and link protein are necessary for their formation and integrity.J. Neurochem.20101145no10.1111/j.1471‑4159.2010.06878.x20584105
     [Google Scholar]
  114. BrücknerG. GroscheJ. Perineuronal nets show intrinsic patterns of extracellular matrix differentiation in organotypic slice cultures.Exp. Brain Res.20011371839310.1007/s00221000061711310175
     [Google Scholar]
  115. BrücknerG. KaczaJ. GroscheJ. Perineuronal nets characterized by vital labelling, confocal and electron microscopy in organotypic slice cultures of rat parietal cortex and hippocampus.J. Mol. Histol.200335211512210.1023/B:HIJO.0000023374.22298.5015328915
     [Google Scholar]
  116. YuZ. HanY. HuD. ChenN. ZhangZ. ChenW. XueY. MengS. LuL. ZhangW. ShiJ. Neurocan regulates vulnerability to stress and the anti-depressant effect of ketamine in adolescent rats.Mol. Psychiatry20222752522253210.1038/s41380‑022‑01495‑w35264728
     [Google Scholar]
  117. CrapserJ.D. SpangenbergE.E. BarahonaR.A. ArreolaM.A. HohsfieldL.A. GreenK.N. Microglia facilitate loss of perineuronal nets in the Alzheimer’s disease brain.EBioMedicine20205810291910.1016/j.ebiom.2020.10291932745992
     [Google Scholar]
  118. MauneyS.A. AthanasK.M. PantazopoulosH. ShaskanN. PasseriE. BerrettaS. WooT.U.W. Developmental pattern of perineuronal nets in the human prefrontal cortex and their deficit in schizophrenia.Biol. Psychiatry201374642743510.1016/j.biopsych.2013.05.00723790226
     [Google Scholar]
  119. KahnR.S. SommerI.E. MurrayR.M. Meyer-LindenbergA. WeinbergerD.R. CannonT.D. O’DonovanM. CorrellC.U. KaneJ.M. van OsJ. InselT.R. Schizophrenia.Nat. Rev. Dis. Primers2015111506710.1038/nrdp.2015.6727189524
     [Google Scholar]
  120. GrandeI. BerkM. BirmaherB. VietaE. Bipolar disorder.Lancet2016387100271561157210.1016/S0140‑6736(15)00241‑X26388529
     [Google Scholar]
  121. MorishitaH. CabungcalJ.H. ChenY. DoK.Q. HenschT.K. Prolonged period of cortical plasticity upon redox dysregulation in fast-spiking interneurons.Biol. Psychiatry201578639640210.1016/j.biopsych.2014.12.02625758057
     [Google Scholar]
  122. CabungcalJ.H. SteulletP. MorishitaH. KraftsikR. CuenodM. HenschT.K. DoK.Q. Perineuronal nets protect fast-spiking interneurons against oxidative stress.Proc. Natl. Acad. Sci.2013110229130913510.1073/pnas.130045411023671099
     [Google Scholar]
  123. CabungcalJ.H. SteulletP. KraftsikR. CuenodM. DoK.Q. Early-life insults impair parvalbumin interneurons via oxidative stress: Reversal by N-acetylcysteine.Biol. Psychiatry201373657458210.1016/j.biopsych.2012.09.02023140664
     [Google Scholar]
  124. LewisD.A. CurleyA.A. GlausierJ.R. VolkD.W. Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia.Trends Neurosci.2012351576710.1016/j.tins.2011.10.00422154068
     [Google Scholar]
  125. EnwrightJF SanapalaS FoglioA BerryR FishKN LewisDA Reduced labeling of parvalbumin neurons and perineuronal nets in the dorsolateral prefrontal cortex of subjects with schizophrenia.Neuropsychopharmacology201641922062214
     [Google Scholar]
  126. PantazopoulosH. MarkotaM. JaquetF. GhoshD. WallinA. SantosA. CatersonB. BerrettaS. Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: A postmortem study on the amygdala.Transl. Psychiatry201551e49610.1038/tp.2014.12825603412
     [Google Scholar]
  127. PantazopoulosH. WooT.U.W. LimM.P. LangeN. BerrettaS. Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia.Arch. Gen. Psychiatry201067215516610.1001/archgenpsychiatry.2009.19620124115
     [Google Scholar]
  128. Schizophrenia Working Group of the Psychiatric Genomics ConsortiumBiological insights from 108 schizophrenia-associated genetic loci.Nature2014511751042142710.1038/nature1359525056061
     [Google Scholar]
  129. CichonS. MühleisenT.W. DegenhardtF.A. MattheisenM. MiróX. StrohmaierJ. SteffensM. MeestersC. HermsS. WeingartenM. PriebeL. HaenischB. AlexanderM. VollmerJ. BreuerR. SchmälC. TessmannP. MoebusS. WichmannH.E. SchreiberS. Müller-MyhsokB. LucaeS. JamainS. LeboyerM. BellivierF. EtainB. HenryC. KahnJ.P. HeathS. HamshereM. O’DonovanM.C. OwenM.J. CraddockN. SchwarzM. VedderH. Kammerer-CierniochJ. ReifA. SasseJ. BauerM. HautzingerM. WrightA. MitchellP.B. SchofieldP.R. MontgomeryG.W. MedlandS.E. GordonS.D. MartinN.G. GustafssonO. AndreassenO. DjurovicS. SigurdssonE. SteinbergS. StefanssonH. StefanssonK. Kapur-PojskicL. OrucL. RivasF. MayoralF. ChuchalinA. BabadjanovaG. TiganovA.S. PantelejevaG. AbramovaL.I. Grigoroiu-SerbanescuM. DiaconuC.C. CzerskiP.M. HauserJ. ZimmerA. LathropM. SchulzeT.G. WienkerT.F. SchumacherJ. MaierW. ProppingP. RietschelM. NöthenM.M. Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder.Am. J. Hum. Genet.201188337238110.1016/j.ajhg.2011.01.01721353194
     [Google Scholar]
  130. MiróX. MeierS. DreisowM.L. FrankJ. StrohmaierJ. BreuerR. SchmälC. AlbayramÖ. Pardo-OlmedillaM.T. MühleisenT.W. DegenhardtF.A. MattheisenM. ReinhardI. Bilkei-GorzoA. CichonS. SeidenbecherC. RietschelM. NöthenM.M. ZimmerA. Studies in humans and mice implicate neurocan in the etiology of mania.Am. J. Psychiatry2012169998299010.1176/appi.ajp.2012.1110158522952076
     [Google Scholar]
  131. SabunciyanS. YolkenR. RaganC.M. PotashJ.B. NimgaonkarV.L. DickersonF. LlenosI.C. WeisS. Polymorphisms in the homeobox geneOTX2 may be a risk factor for bipolar disorder.Am. J. Med. Genet. B. Neuropsychiatr. Genet.2007144B81083108610.1002/ajmg.b.3052317541950
     [Google Scholar]
  132. DoK.Q. CuenodM. HenschT.K. Targeting oxidative stress and aberrant critical period plasticity in the developmental trajectory to schizophrenia.Schizophr. Bull.201541483584610.1093/schbul/sbv06526032508
     [Google Scholar]
  133. DwirD. GiangrecoB. XinL. TenenbaumL. CabungcalJ.H. SteulletP. GoupilA. CleusixM. JenniR. ChtartoA. BaumannP.S. KlauserP. ConusP. TirouvanziamR. CuenodM. DoK.Q. MMP9/RAGE pathway overactivation mediates redox dysregulation and neuroinflammation, leading to inhibitory/excitatory imbalance: A reverse translation study in schizophrenia patients.Mol. Psychiatry202025112889290410.1038/s41380‑019‑0393‑530911107
     [Google Scholar]
  134. SteulletP. CabungcalJ-H. BukhariS.A. ArdeltM.I. PantazopoulosH. HamatiF. SaltT.E. CuenodM. DoK.Q. BerrettaS. The thalamic reticular nucleus in schizophrenia and bipolar disorder: Role of parvalbumin-expressing neuron networks and oxidative stress.Mol. Psychiatry201823102057206510.1038/mp.2017.23029180672
     [Google Scholar]
  135. SuttkusA. MorawskiM. ArendtT. Protective properties of neural extracellular matrix.Mol. Neurobiol.2016531738210.1007/s12035‑014‑8990‑425404091
     [Google Scholar]
  136. SethiM.K. ZaiaJ. Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease.Anal. Bioanal. Chem.2017409237939410.1007/s00216‑016‑9900‑627601046
     [Google Scholar]
  137. SuttkusA. HolzerM. MorawskiM. ArendtT. The neuronal extracellular matrix restricts distribution and internalization of aggregated Tau-protein.Neuroscience201631322523510.1016/j.neuroscience.2015.11.04026621125
     [Google Scholar]
  138. SuttkusA. RohnS. WeigelS. GlöcknerP. ArendtT. MorawskiM. Aggrecan, link protein and tenascin-R are essential components of the perineuronal net to protect neurons against iron-induced oxidative stress.Cell Death Dis.201453e111910.1038/cddis.2014.2524625978
     [Google Scholar]
  139. CarulliD. BroersenR. de WinterF. MuirE.M. MeškovićM. de WaalM. de VriesS. BoeleH.J. CantoC.B. De ZeeuwC.I. VerhaagenJ. Cerebellar plasticity and associative memories are controlled by perineuronal nets.Proc. Natl. Acad. Sci.2020117126855686510.1073/pnas.191616311732152108
     [Google Scholar]
  140. DubisovaJ. BurianovaJ.S. SvobodovaL. MakovickyP. Martinez-VareaN. CimpeanA. FawcettJ.W. KwokJ.C.F. KubinovaS. Oral treatment of 4-methylumbelliferone reduced perineuronal nets and improved recognition memory in mice.Brain Res. Bull.202218114415610.1016/j.brainresbull.2022.01.01135066096
     [Google Scholar]
  141. RigaD. KramvisI. KoskinenM.K. van BokhovenP. van der HarstJ.E. HeistekT.S. Jaap TimmermanA. van NieropP. van der SchorsR.C. PienemanA.W. de WegerA. van MourikY. SchoffelmeerA.N.M. MansvelderH.D. MeredithR.M. HoogendijkW.J.G. SmitA.B. SpijkerS. Hippocampal extracellular matrix alterations contribute to cognitive impairment associated with a chronic depressive-like state in rats.Sci. Transl. Med.20179421eaai875310.1126/scitranslmed.aai875329263233
     [Google Scholar]
  142. DomínguezS. ReyC.C. TherreauL. FantonA. MassotteD. VerretL. PiskorowskiR.A. ChevaleyreV. Maturation of PNN and ErbB4 Signaling in Area CA2 during adolescence underlies the emergence of PV interneuron plasticity and social memory.Cell Rep.201929510991112.e410.1016/j.celrep.2019.09.04431665627
     [Google Scholar]
  143. CopeE.C. ZychA.D. KatchurN.J. WatersR.C. LahamB.J. DiethornE.J. Atypical perineuronal nets in the CA2 region interfere with social memory in a mouse model of social dysfunction.Mol. Psychiatry202120212783520353134183768
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673258290231009111633
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Perineuronal Nets: From Structure to Neurological Disorders
Curr. Med. Chem. 32, 1685 (2025); https://doi.org/10.2174/0109298673258290231009111633
/content/journals/cmc/10.2174/0109298673258290231009111633
/content/journals/cmc/10.2174/0109298673258290231009111633
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  • Article Type:     Review Article
Keyword(s): Alzheimer's disease; extracellular matrix; memory; neurological disorders; Perineuronal nets; plasticity

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