Skip to main content

Wnt-7a Stimulates Dendritic Spine Morphogenesis and PSD-95 Expression Through Canonical Signaling

Molecular Neurobiology volume 56, pages 1870–1882 (2019)Cite this article

Abstract

Wnt signaling regulates brain development and synapse maturation; however, the precise molecular mechanism remains elusive. Here, we report that Wnt-7a stimulates dendritic spine morphogenesis in the hippocampus via glycogen synthase kinase-3 β (GSK-3β) inhibition, triggering β-catenin/T cell factor/lymphoid enhancer factor (TCF/LEF)-dependent gene transcription and promoting postsynaptic density-95 (PSD-95) protein expression. In addition, wild-type mice treated with an inhibitor of β-catenin/TCF/LEF-mediated transcription showed a reduction in spatial memory acquisition accompanied by a reduction in PSD-95 and decreases in spine density measured by Golgi staining, suggesting that PSD-95 is a novel Wnt target gene. Together, our data strongly demonstrate that Wnt-dependent target gene transcription is essential to hippocampal synaptic plasticity.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

References

  1. Inestrosa NC, Arenas E (2010) Emerging roles of Wnts in the adult nervous system. Nat Rev Neurosci 11(2):77–86. https://doi.org/10.1038/nrn2755

    CAS  Article  Google Scholar 

  2. Budnik V, Salinas PC (2011) Wnt signaling during synaptic development and plasticity. Curr Opin Neurobiol 21(1):151–159. https://doi.org/10.1016/j.conb.2010.12.002

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Inestrosa NC, Montecinos-Oliva C, Fuenzalida M (2012) Wnt signaling: role in Alzheimer disease and schizophrenia. J NeuroImmune Pharmacol 7(4):788–807. https://doi.org/10.1007/s11481-012-9417-5

    Article  PubMed  Google Scholar 

  4. Wang J, Zhu G, Huang L, Nie T, Tao K, Li Y, Gao G (2017) Morphine administration induces change in anxiety-related behavior via Wnt/beta-catenin signaling. Neurosci Lett 639:199–206. https://doi.org/10.1016/j.neulet.2017.01.005

    CAS  Article  PubMed  Google Scholar 

  5. Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810. https://doi.org/10.1146/annurev.cellbio.20.010403.113126

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Arrazola MS, Varela-Nallar L, Colombres M, Toledo EM, Cruzat F, Pavez L, Assar R, Aravena A et al (2009) Calcium/calmodulin-dependent protein kinase type IV is a target gene of the Wnt/beta-catenin signaling pathway. J Cell Physiol 221(3):658–667. https://doi.org/10.1002/jcp.21902

    CAS  Article  PubMed  Google Scholar 

  7. Kuhl M, Sheldahl LC, Park M, Miller JR, Moon RT (2000) The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet 16(7):279–283

    CAS  Article  PubMed  Google Scholar 

  8. Nagaoka T, Ohashi R, Inutsuka A, Sakai S, Fujisawa N, Yokoyama M, Huang YH, Igarashi M et al (2014) The Wnt/planar cell polarity pathway component Vangl2 induces synapse formation through direct control of N-cadherin. Cell Rep 6(5):916–927. https://doi.org/10.1016/j.celrep.2014.01.044

    CAS  Article  PubMed  Google Scholar 

  9. Varela-Nallar L, Alfaro IE, Serrano FG, Parodi J, Inestrosa NC (2010) Wingless-type family member 5A (Wnt-5a) stimulates synaptic differentiation and function of glutamatergic synapses. Proc Natl Acad Sci U S A 107(49):21164–21169. https://doi.org/10.1073/pnas.1010011107

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ramirez VT, Ramos-Fernandez E, Henriquez JP, Lorenzo A, Inestrosa NC (2016) Wnt-5a/Frizzled9 receptor signaling through the G alpha(o)-G beta gamma complex regulates dendritic spine formation. J Biol Chem 291(36):19092–19107. https://doi.org/10.1074/jbc.M116.722132

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Farias GG, Alfaro IE, Cerpa W, Grabowski CP, Godoy JA, Bonansco C, Inestrosa NC (2009) Wnt-5a/JNK signaling promotes the clustering of PSD-95 in hippocampal neurons. J Biol Chem 284(23):15857–15866. https://doi.org/10.1074/jbc.M808986200

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Chen J, Park CS, Tang SJ (2006) Activity-dependent synaptic Wnt release regulates hippocampal long term potentiation. J Biol Chem 281(17):11910–11916. https://doi.org/10.1074/jbc.M511920200

    CAS  Article  PubMed  Google Scholar 

  13. Cerpa W, Godoy JA, Alfaro I, Farias GG, Metcalfe MJ, Fuentealba R, Bonansco C, Inestrosa NC (2008) Wnt-7a modulates the synaptic vesicle cycle and synaptic transmission in hippocampal neurons. J Biol Chem 283(9):5918–5927. https://doi.org/10.1074/jbc.M705943200

    CAS  Article  PubMed  Google Scholar 

  14. Ciani L, Marzo A, Boyle K, Stamatakou E, Lopes DM, Anane D, McLeod F, Rosso SB et al (2015) Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1. Nat Commun 6:8302. https://doi.org/10.1038/ncomms9302

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Tabatadze N, Tomas C, McGonigal R, Lin B, Schook A, Routtenberg A (2012) Wnt transmembrane signaling and long-term spatial memory. Hippocampus 22(6):1228–1241. https://doi.org/10.1002/hipo.20991

    CAS  Article  PubMed  Google Scholar 

  16. Ochs SM, Dorostkar MM, Aramuni G, Schon C, Filser S, Poschl J, Kremer A, Van Leuven F et al (2015) Loss of neuronal GSK3beta reduces dendritic spine stability and attenuates excitatory synaptic transmission via beta-catenin. Mol Psychiatry 20(4):482–489. https://doi.org/10.1038/mp.2014.55

    CAS  Article  PubMed  Google Scholar 

  17. Tapia-Rojas C, Schuller A, Lindsay CB, Ureta RC, Mejias-Reyes C, Hancke J, Melo F, Inestrosa NC (2015) Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3beta: autoregulation of GSK-3beta in vivo. Biochem J 466(2):415–430. https://doi.org/10.1042/BJ20140207

    CAS  Article  PubMed  Google Scholar 

  18. Serrano FG, Tapia-Rojas C, Carvajal FJ, Hancke J, Cerpa W, Inestrosa NC (2014) Andrographolide reduces cognitive impairment in young and mature AbetaPPswe/PS-1 mice. Mol Neurodegener 9:61. https://doi.org/10.1186/1750-1326-9-61

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Marzo A, Galli S, Lopes D, McLeod F, Podpolny M, Segovia-Roldan M, Ciani L, Purro S et al (2016) Reversal of synapse degeneration by restoring Wnt signaling in the adult hippocampus. Curr Biol 26(19):2551–2561. https://doi.org/10.1016/j.cub.2016.07.024

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Fortress AM, Schram SL, Tuscher JJ, Frick KM (2013) Canonical Wnt signaling is necessary for object recognition memory consolidation. J Neurosci 33(31):12619–12626. https://doi.org/10.1523/JNEUROSCI.0659-13.2013

    CAS  Article  PubMed  Google Scholar 

  21. Ciani L, Boyle KA, Dickins E, Sahores M, Anane D, Lopes DM, Gibb AJ, Salinas PC (2011) Wnt7a signaling promotes dendritic spine growth and synaptic strength through Ca(2)(+)/Calmodulin-dependent protein kinase II. Proc Natl Acad Sci U S A 108(26):10732–10737. https://doi.org/10.1073/pnas.1018132108

    Article  PubMed  PubMed Central  Google Scholar 

  22. Caceres A, Binder LI, Payne MR, Bender P, Rebhun L, Steward O (1984) Differential subcellular localization of tubulin and the microtubule-associated protein MAP2 in brain tissue as revealed by immunocytochemistry with monoclonal hybridoma antibodies. J Neurosci 4(2):394–410

    CAS  Article  PubMed  Google Scholar 

  23. Tapia-Rojas C, Burgos PV, Inestrosa NC (2016) Inhibition of Wnt signaling induces amyloidogenic processing of amyloid precursor protein and the production and aggregation of Amyloid-beta (Abeta)42 peptides. J Neurochem 139(6):1175–1191. https://doi.org/10.1111/jnc.13873

    CAS  Article  PubMed  Google Scholar 

  24. van de Wetering M, Cavallo R, Dooijes D, van Beest M, van Es J, Loureiro J, Ypma A, Hursh D et al (1997) Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88(6):789–799

    Article  PubMed  Google Scholar 

  25. Tapia-Rojas C, Lindsay CB, Montecinos-Oliva C, Arrazola MS, Retamales RM, Bunout D, Hirsch S, Inestrosa NC (2015) Is L-methionine a trigger factor for Alzheimer’s-like neurodegeneration?: Changes in Abeta oligomers, tau phosphorylation, synaptic proteins, Wnt signaling and behavioral impairment in wild-type mice. Mol Neurodegener 10:62. https://doi.org/10.1186/s13024-015-0057-0

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Koyama Y, Tohyama M (2012) A modified and highly sensitive Golgi-Cox method to enable complete and stable impregnation of embryonic neurons. J Neurosci Methods 209(1):58–61. https://doi.org/10.1016/j.jneumeth.2012.06.007

    Article  PubMed  Google Scholar 

  27. Niehrs C (2006) Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene 25(57):7469–7481. https://doi.org/10.1038/sj.onc.1210054

    CAS  Article  PubMed  Google Scholar 

  28. Cross DA, Culbert AA, Chalmers KA, Facci L, Skaper SD, Reith AD (2001) Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death. J Neurochem 77(1):94–102

    CAS  Article  PubMed  Google Scholar 

  29. Inestrosa NC, Varela-Nallar L (2015) Wnt signalling in neuronal differentiation and development. Cell Tissue Res 359(1):215–223. https://doi.org/10.1007/s00441-014-1996-4

    CAS  Article  PubMed  Google Scholar 

  30. Emami KH, Nguyen C, Ma H, Kim DH, Jeong KW, Eguchi M, Moon RT, Teo JL et al (2004) A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected]. Proc Natl Acad Sci U S A 101(34):12682–12687. https://doi.org/10.1073/pnas.0404875101

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. Yousif NG, Hadi NR, Hassan AM (2017) Indocyanine Green-001 (ICG-001) attenuates Wnt/beta-catenin-induces myocardial injury following sepsis. J Pharmacol Pharmacother 8(1):14–20. https://doi.org/10.4103/jpp.JPP_153_16

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Risher WC, Ustunkaya T, Singh Alvarado J, Eroglu C (2014) Rapid Golgi analysis method for efficient and unbiased classification of dendritic spines. PLoS One 9(9):e107591. https://doi.org/10.1371/journal.pone.0107591

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. von Bohlen, Halbach O, Zacher C, Gass P, Unsicker K (2006) Age-related alterations in hippocampal spines and deficiencies in spatial memory in mice. J Neurosci Res 83(4):525–531. https://doi.org/10.1002/jnr.20759

    CAS  Article  Google Scholar 

  34. Chen G, Chen KS, Knox J, Inglis J, Bernard A, Martin SJ, Justice A, McConlogue L et al (2000) A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer’s disease. Nature 408(6815):975–979. https://doi.org/10.1038/35050103

    CAS  Article  Google Scholar 

  35. Tapia-Rojas C, Inestrosa NC (2017) Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer’s disease in J20-APP transgenic and wild-type mice. https://doi.org/10.1111/jnc.14278

  36. Clevers H, Nusse R (2012) Wnt/beta-catenin signaling and disease. Cell 149(6):1192–1205. https://doi.org/10.1016/j.cell.2012.05.012

    CAS  Article  PubMed  Google Scholar 

  37. Jamieson C, Sharma M, Henderson BR (2012) Wnt signaling from membrane to nucleus: beta-catenin caught in a loop. Int J Biochem Cell Biol 44(6):847–850. https://doi.org/10.1016/j.biocel.2012.03.001

    CAS  Article  Google Scholar 

  38. Cadigan KM, Waterman ML (2012) TCF/LEFs and Wnt signaling in the nucleus. Cold Spring Harb Perspect Biol 4 (11). https://doi.org/10.1101/cshperspect.a007906

  39. Inestrosa NC, Varela-Nallar L (2014) Wnt signaling in the nervous system and in Alzheimer’s disease. J Mol Cell Biol 6(1):64–74. https://doi.org/10.1093/jmcb/mjt051

    Article  Google Scholar 

  40. Hall AC, Lucas FR, Salinas PC (2000) Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling. Cell 100(5):525–535

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. Lucas FR, Salinas PC (1997) WNT-7a induces axonal remodeling and increases synapsin I levels in cerebellar neurons. Dev Biol 192(1):31–44. https://doi.org/10.1006/dbio.1997.8734

    CAS  Article  Google Scholar 

  42. Farias GG, Valles AS, Colombres M, Godoy JA, Toledo EM, Lukas RJ, Barrantes FJ, Inestrosa NC (2007) Wnt-7a induces presynaptic colocalization of alpha 7-nicotinic acetylcholine receptors and adenomatous polyposis coli in hippocampal neurons. J Neurosci 27(20):5313–5325. https://doi.org/10.1523/JNEUROSCI.3934-06.2007

    CAS  Article  PubMed  Google Scholar 

  43. Wu D, Pan W (2009) GSK3: a multifaceted kinase in Wnt signaling. Trends Biochem Sci 35(3):161–168. https://doi.org/10.1016/j.tibs.2009.10.002

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. Oliva C, Vargas J, Inestrosa N (2013) Wnt signaling: role in LTP, neural networks and memory. Ageing Res Rev 12(3):786–800

    CAS  Article  PubMed  Google Scholar 

  45. Beique JC, Lin DT, Kang MG, Aizawa H, Takamiya K, Huganir RL (2006) Synapse-specific regulation of AMPA receptor function by PSD-95. Proc Natl Acad Sci USA 103(51):19535–19540. https://doi.org/10.1073/pnas.0608492103

    CAS  Article  PubMed  Google Scholar 

  46. Elias GM, Funke L, Stein V, Grant SG, Bredt DS, Nicoll RA (2006) Synapse-specific and developmentally regulated targeting of AMPA receptors by a family of MAGUK scaffolding proteins. Neuron 52(2):307–320. https://doi.org/10.1016/j.neuron.2006.09.012

    CAS  Article  PubMed  Google Scholar 

  47. Speese S, Budnik V (2007) Wnts: up-and-coming at the synapse. Trends Neurosci 30(6):268–275

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. Oliva CA, Inestrosa NC (2015) A novel function for Wnt signaling modulating neuronal firing activity and the temporal structure of spontaneous oscillation in the entorhinal-hippocampal circuit. Exp Neurol 269:43–55. https://doi.org/10.1016/j.expneurol.2015.03.027

    CAS  Article  PubMed  Google Scholar 

  49. Hooper C, Markevich V, Plattner F, Killick R, Schofield E, Engel T, Hernandez F, Anderton B et al (2007) Glycogen synthase kinase-3 inhibition is integral to long-term potentiation. Eur J Neurosci 25(1):81–86. https://doi.org/10.1111/j.1460-9568.2006.05245.x

    Article  PubMed  Google Scholar 

  50. Peineau S, Taghibiglou C, Bradley C, Wong TP, Liu L, Lu J, Lo E, Wu D et al (2007) LTP inhibits LTD in the hippocampus via regulation of GSK3beta. Neuron 53(5):703–717. https://doi.org/10.1016/j.neuron.2007.01.029

    CAS  Article  PubMed  Google Scholar 

  51. Mahmmoud RR, Sase S, Aher YD, Sase A, Groger M, Mokhtar M, Hoger H, Lubec G (2015) Spatial and working memory is linked to spine density and mushroom spines. PLoS One 10(10):e0139739. https://doi.org/10.1371/journal.pone.0139739

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  52. Leuner B, Falduto J, Shors TJ (2003) Associative memory formation increases the observation of dendritic spines in the hippocampus. J Neurosci 23(2):659–665

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. Jedlicka P, Vlachos A, Schwarzacher SW, Deller T (2008) A role for the spine apparatus in LTP and spatial learning. Behav Brain Res 192(1):12–19. https://doi.org/10.1016/j.bbr.2008.02.033

    Article  PubMed  Google Scholar 

  54. Beltran-Campos V, Prado-Alcala RA, Leon-Jacinto U, Aguilar-Vazquez A, Quirarte GL, Ramirez-Amaya V, Diaz-Cintra S (2011) Increase of mushroom spine density in CA1 apical dendrites produced by water maze training is prevented by ovariectomy. Brain Res 1369:119–130. https://doi.org/10.1016/j.brainres.2010.10.105

    CAS  Article  PubMed  Google Scholar 

  55. Moser MB, Trommald M, Andersen P (1994) An increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses. Proc Natl Acad Sci U S A 91(26):12673–12675

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. Fiala JC, Spacek J, Harris KM (2002) Dendritic spine pathology: cause or consequence of neurological disorders? Brain Res Brain Res Rev 39(1):29–54

    Article  PubMed  Google Scholar 

  57. Ehrlich I, Malinow R (2004) Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity. J Neurosci 24(4):916–927. https://doi.org/10.1523/JNEUROSCI.4733-03.2004

    CAS  Article  PubMed  Google Scholar 

  58. Fitzgerald PJ, Pinard CR, Camp MC, Feyder M, Sah A, Bergstrom HC, Graybeal C, Liu Y et al (2015) Durable fear memories require PSD-95. Mol Psychiatry 20(7):901–912. https://doi.org/10.1038/mp.2014.161

    CAS  Article  PubMed  Google Scholar 

  59. Nagura H, Ishikawa Y, Kobayashi K, Takao K, Tanaka T, Nishikawa K, Tamura H, Shiosaka S et al (2012) Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice. Mol Brain 5:43. https://doi.org/10.1186/1756-6606-5-43

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. Vargas JY, Fuenzalida M, Inestrosa NC (2014) In vivo activation of Wnt signaling pathway enhances cognitive function of adult mice and reverses cognitive deficits in an Alzheimer’s disease model. J Neurosci 34(6):2191–2202. https://doi.org/10.1523/JNEUROSCI.0862-13.2014

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Dr. Caitlin S. M. Cowan (University College Cork, Ireland) for her contribution to the final version of the manuscript and Gloria Méndez for preparing the primary rat culture of hippocampal neurons. This work was supported by grants AFB 170005 and CONICYT-PFB no. 12/2007 from the Basal Center for Excellence in Science and Technology and by Fondecyt no. 1120156 to NCI, as well as by a predoctoral fellowship from the Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) to V.T.R and C.T-R and postdoctoral fellowship Fondecyt Postdoctorado no. 3140355 to E.R-F.

Author information

Affiliations

  1. Centro de Envejecimiento y Regeneración (CARE UC), Laboratorio de Neurobiología Molecular, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica, 8331150, Santiago, Chile

    Eva Ramos-Fernández, Cheril Tapia-Rojas, Valerie T. Ramírez & Nibaldo C. Inestrosa

  2. Center for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia

    Nibaldo C. Inestrosa

  3. Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, 6200000, Punta Arenas, Chile

    Nibaldo C. Inestrosa

Authors
  1. Eva Ramos-Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cheril Tapia-Rojas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valerie T. Ramírez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nibaldo C. Inestrosa
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NIC, CTR, VTR, and ERF designed the experiments and participated in the preparation of the manuscript. VTR performed the GFP transfections and confocal images, analyzed and interpreted results, and wrote the manuscript. CTR performed most of the Western blots, mouse injections, behavioral test analysis, and interpretation of results and wrote the manuscript. ER-F performed GFP transfections, immunofluorescence experiments, Western blots, mouse injections, and Golgi staining, analyzed and interpreted results, composed the figures, and organized the final manuscript. NIC supervised the experiments and participated in the discussion of the results.

Corresponding author

Correspondence to Nibaldo C. Inestrosa.

Ethics declarations

The Bioethical and Biosafety Committee of the Faculty of Biological Sciences of the Pontificia Universidad Católica de Chile approved the experimental culture procedures, animal treatments and behavioral experiments.

Conflicts of Interest

The authors declare that they have no competing interests.

Electronic Supplementary Material

Supplementary Figure 1
figure 9

Dkk-1 and ICG treatments reduce c-Jun expression (a target gene of the Wnt canonical pathway) in hippocampal neurons. Quantification of the immunoblot in Fig. 5c showing c-Jun levels relative to the amount of β-tubulin (n = 3) *** p < 0.001; **, p < 0.01(PNG 441 kb)

Full size image

High resolution image (TIF 9587 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ramos-Fernández, E., Tapia-Rojas, C., Ramírez, V.T. et al. Wnt-7a Stimulates Dendritic Spine Morphogenesis and PSD-95 Expression Through Canonical Signaling. Mol Neurobiol 56, 1870–1882 (2019). https://doi.org/10.1007/s12035-018-1162-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-018-1162-1

Keywords

  • Wnt signaling
  • Dendritic spine plasticity
  • PSD-95
  • TCF/LEF