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Tumor suppressor p53 modulates activity-dependent synapse strengthening, autism-like behavior and hippocampus-dependent learning

Molecular Psychiatry (2023)Cite this article

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Abstract

Synaptic potentiation underlies various forms of behavior and depends on modulation by multiple activity-dependent transcription factors to coordinate the expression of genes necessary for sustaining synaptic transmission. Our current study identified the tumor suppressor p53 as a novel transcription factor involved in this process. We first revealed that p53 could be elevated upon chemically induced long-term potentiation (cLTP) in cultured primary neurons. By knocking down p53 in neurons, we further showed that p53 is required for cLTP-induced elevation of surface GluA1 and GluA2 subunits of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Because LTP is one of the principal plasticity mechanisms underlying behaviors, we employed forebrain-specific knockdown of p53 to evaluate the role of p53 in behavior. Our results showed that, while knocking down p53 in mice does not alter locomotion or anxiety-like behavior, it significantly promotes repetitive behavior and reduces sociability in mice of both sexes. In addition, knocking down p53 also impairs hippocampal LTP and hippocampus-dependent learning and memory. Most importantly, these learning-associated defects are more pronounced in male mice than in female mice, suggesting a sex-specific role of p53 in these behaviors. Using RNA sequencing (RNAseq) to identify p53-associated genes in the hippocampus, we showed that knocking down p53 up- or down-regulates multiple genes with known functions in synaptic plasticity and neurodevelopment. Altogether, our study suggests p53 as an activity-dependent transcription factor that mediates the surface expression of AMPAR, permits hippocampal synaptic plasticity, represses autism-like behavior, and promotes hippocampus-dependent learning and memory.

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Fig. 1: p53 protein expression is induced by cLTP.
Fig. 2: Knocking down p53 impairs cLTP-induced surface expression of AMPAR and strengthening of synapses.
Fig. 3: Knocking down p53 does not alter locomotor activity or anxiety-like behavior in mice.
Fig. 4: Knocking down p53 increases repetitive behavior and reduces sociability in mice.
Fig. 5: Knocking down p53 impairs hippocampus-dependent learning and memory particularly in male mice.
Fig. 6: RNAseq reveals p53-associated genes potentially involved in synaptic plasticity, learning and memory.

Data availability

The RNA sequencing results can be found at https://doi.org/10.6084/m9.figshare.23560812.v1.

References

  1. Hong EJ, McCord AE, Greenberg ME. A biological function for the neuronal activity-dependent component of Bdnf transcription in the development of cortical inhibition. Neuron. 2008;60:610–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tsai NP, Wilkerson JR, Guo W, Maksimova MA, DeMartino GN, Cowan CW, et al. Multiple autism-linked genes mediate synapse elimination via proteasomal degradation of a synaptic scaffold PSD-95. Cell. 2012;151:1581–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ramanan N, Shen Y, Sarsfield S, Lemberger T, Schütz G, Linden DJ, et al. SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability. Nat Neurosci. 2005;8:759–67.

    Article  CAS  PubMed  Google Scholar 

  4. Faust TE, Gunner G, Schafer DP. Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS. Nat Rev Neurosci. 2021;22:657–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kastenhuber ER, Lowe SW. Putting p53 in context. Cell. 2017;170:1062–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Camins A, Verdaguer E, Folch J, Beas-Zarate C, Canudas AM, Pallas M.Inhibition of ataxia telangiectasia-p53-E2F-1 pathway in neurons as a target for the prevention of neuronal apoptosis.Curr Drug Metab. 2007;8:709–15.

    Article  CAS  PubMed  Google Scholar 

  7. Folch J, Junyent F, Verdaguer E, Auladell C, Pizarro JG, Beas-Zarate C, et al. Role of cell cycle re-entry in neurons: a common apoptotic mechanism of neuronal cell death. Neurotox Res. 2012;22:195–207.

    Article  PubMed  Google Scholar 

  8. Simon DJ, Belsky DM, Bowen ME, Ohn CYJ, O’Rourke MK, Shen R, et al. An anterograde pathway for sensory axon degeneration gated by a cytoplasmic action of the transcriptional regulator P53. Dev Cell. 2021;56:976–84.e3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Slomnicki LP, Pietrzak M, Vashishta A, Jones J, Lynch N, Elliot S, et al. Requirement of neuronal ribosome synthesis for growth and maintenance of the dendritic tree. J Biol Chem. 2016;291:5721–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Liu DC, Lee KY, Lizarazo S, Cook JK, Tsai NP. ER stress-induced modulation of neural activity and seizure susceptibility is impaired in a fragile X syndrome mouse model. Neurobiol Dis. 2021;158:105450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liu DC, Soriano S, Yook Y, Lizarazo S, Eagleman DE, Tsai NP. Chronic activation of Gp1 mGluRs leads to distinct refinement of neural network activity through non-canonical p53 and Akt signaling. eNeuro. 2020;7:ENEURO.0438-19.

  12. Lee KY, Jewett KA, Chung HJ, Tsai NP. Loss of Fragile X Protein FMRP impairs homeostatic synaptic downscaling through tumor Suppressor p53 and Ubiquitin E3 Ligase Nedd4-2. Hum Mol Genet. 2018;27:2805–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Levy OA, Malagelada C, Greene LA. Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps. Apoptosis. 2009;14:478–500.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Miller FD, Pozniak CD, Walsh GS. Neuronal life and death: an essential role for the p53 family. Cell Death Differ. 2000;7:880–8.

    Article  CAS  PubMed  Google Scholar 

  15. Fortin DA, Davare MA, Srivastava T, Brady JD, Nygaard S, Derkach VA, et al. Long-term potentiation-dependent spine enlargement requires synaptic Ca2+-permeable AMPA receptors recruited by CaM-kinase I. J Neurosci. 2010;30:11565–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hussain NK, Diering GH, Sole J, Anggono V, Huganir RL. Sorting Nexin 27 regulates basal and activity-dependent trafficking of AMPARs. Proc Natl Acad Sci USA. 2014;111:11840–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bouwknecht JA, Spiga F, Staub DR, Hale MW, Shekhar A, Lowry CA. Differential effects of exposure to low-light or high-light open-field on anxiety-related behaviors: relationship to c-Fos expression in serotonergic and non-serotonergic neurons in the dorsal raphe nucleus. Brain Res Bull. 2007;72:32–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kastenberger I, Lutsch C, Herzog H, Schwarzer C. Influence of sex and genetic background on anxiety-related and stress-induced behaviour of prodynorphin-deficient mice. PLoS One. 2012;7:e34251.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Puschban Z, Sah A, Grutsch I, Singewald N, Dechant G. Reduced anxiety-like behavior and altered hippocampal morphology in female p75NTR(exon IV-/-) mice. Front Behav Neurosci. 2016;10:103.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wang H, Aragam B, Xing EP. Trade-offs of linear mixed models in genome-Wide Association Studies. J Comput Biol. 2022;29:233–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Satterstrom FK, Kosmicki JA, Wang J, Breen MS, De Rubeis S, An JY, et al. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell. 2020;180:568–84.e23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lee KY, Zhu J, Cutia CA, Christian-Hinman CA, Rhodes JS, Tsai NP. Infantile spasms-linked Nedd4-2 mediates hippocampal plasticity and learning via cofilin signaling. EMBO Rep. 2021;22:e52645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bourdon JC, Fernandes K, Murray-Zmijewski F, Liu G, Diot A, Xirodimas DP, et al. p53 isoforms can regulate p53 transcriptional activity. Genes Dev. 2005;19:2122–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Loughery J, Cox M, Smith LM, Meek DW. Critical role for p53-serine 15 phosphorylation in stimulating transactivation at p53-responsive promoters. Nucleic Acids Res. 2014;42:7666–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Turenne GA, Price BD. Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53’s transcriptional activity. BMC Cell Biol. 2001;2:12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Colledge M, Snyder EM, Crozier RA, Soderling JA, Jin Y, Langeberg LK, et al. Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression. Neuron. 2003;40:595–607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tang SJ, Reis G, Kang H, Gingras AC, Sonenberg N, Schuman EM. A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus. Proc Natl Acad Sci USA. 2002;99:467–72.

    Article  CAS  PubMed  Google Scholar 

  28. Gorski JA, Talley T, Qiu M, Puelles L, Rubenstein JL, Jones KR. Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J Neurosci. 2002;22:6309–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Fortin A, Cregan SP, MacLaurin JG, Kushwaha N, Hickman ES, Thompson CS, et al. APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death. J Cell Biol. 2001;155:207–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jaafari N, Henley JM, Hanley JG. PICK1 mediates transient synaptic expression of GluA2-lacking AMPA receptors during glycine-induced AMPA receptor trafficking. J Neurosci. 2012;32:11618–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang M, Ramasamy VS, Kang HK, Jo J. Oleuropein promotes hippocampal LTP via intracellular calcium mobilization and Ca(2+)-permeable AMPA receptor surface recruitment. Neuropharmacology. 2020;176:108196.

    Article  CAS  PubMed  Google Scholar 

  32. Yap KA, Shetty MS, Garcia-Alvarez G, Lu B, Alagappan D, Oh-Hora M, et al. STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses. Neurobiol Learn Mem. 2017;138:54–61.

    Article  CAS  PubMed  Google Scholar 

  33. Kim YJ, Khoshkhoo S, Frankowski JC, Zhu B, Abbasi S, Lee S, et al. Chd2 is necessary for neural circuit development and long-term memory. Neuron. 2018;100:1180–93.e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Leach PT, Poplawski SG, Kenney JW, Hoffman B, Liebermann DA, Abel T, et al. Gadd45b knockout mice exhibit selective deficits in hippocampus-dependent long-term memory. Learn Mem. 2012;19:319–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Seese RR, Maske AR, Lynch G, Gall CM. Long-term memory deficits are associated with elevated synaptic ERK1/2 activation and reversed by mGluR5 antagonism in an animal model of autism. Neuropsychopharmacology. 2014;39:1664–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Rahman MR, Petralia MC, Ciurleo R, Bramanti A, Fagone P, Shahjaman M, et al. Comprehensive analysis of RNA-Seq gene expression profiling of brain transcriptomes reveals novel genes, regulators, and pathways in autism spectrum disorder. Brain Sci. 2020;10:747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hurley S, Mohan C, Suetterlin P, Ellingford R, Riegman KLH, Ellegood J, et al. Distinct, dosage-sensitive requirements for the autism-associated factor CHD8 during cortical development. Mol Autism. 2021;12:16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Thomas A, Burant A, Bui N, Graham D, Yuva-Paylor LA, Paylor R. Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety. Psychopharmacology. 2009;204:361–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Nicoll RA. A brief history of long-term potentiation. Neuron. 2017;93:281–90.

    Article  CAS  PubMed  Google Scholar 

  40. Sudhof TC, Malenka RC. Understanding synapses: past, present, and future. Neuron. 2008;60:469–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ujjainwala AL, Courtney CD, Wojnowski NM, Rhodes JS, Christian CA. Differential impacts on multiple forms of spatial and contextual memory in diazepam binding inhibitor knockout mice. J Neurosci Res. 2019;97:683–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Heglind M, Cederberg A, Aquino J, Lucas G, Ernfors P, Enerbäck S. Lack of the central nervous system- and neural crest-expressed forkhead gene Foxs1 affects motor function and body weight. Mol Cell Biol. 2005;25:5616–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Chen YJ, Deng SM, Chen HW, Tsao CH, Chen WT, Cheng SJ, et al. Follistatin mediates learning and synaptic plasticity via regulation of Asic4 expression in the hippocampus. Proc Natl Acad Sci USA. 2021;118:e2109040118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cong Q, Soteros BM, Wollet M, Kim JH, Sia GM. The endogenous neuronal complement inhibitor SRPX2 protects against complement-mediated synapse elimination during development. Nat Neurosci. 2020;23:1067–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jay P, Rougeulle C, Massacrier A, Moncla A, Mattei MG, Malzac P, et al. The human necdin gene, NDN, is maternally imprinted and located in the Prader-Willi syndrome chromosomal region. Nat Genet. 1997;17:357–61.

    Article  CAS  PubMed  Google Scholar 

  46. Asai T, Liu Y, Di Giandomenico S, Bae N, Ndiaye-Lobry D, Deblasio A, et al. Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells. Blood. 2012;120:1601–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. MacDonald HR, Wevrick R. The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse. Hum Mol Genet. 1997;6:1873–8.

    Article  CAS  PubMed  Google Scholar 

  48. Wu RN, Hung WC, Chen CT, Tsai LP, Lai WS, Min MY, et al. Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader-Willi syndrome. J Neurodev Disord. 2020;12:21.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Kuwajima T, Hasegawa K, Yoshikawa K. Necdin promotes tangential migration of neocortical interneurons from basal forebrain. J Neurosci. 2010;30:3709–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Miller NL, Wevrick R, Mellon PL. Necdin, a Prader-Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development. Hum Mol Genet. 2009;18:248–60.

    Article  CAS  PubMed  Google Scholar 

  51. Karge A, Bonar NA, Wood S, Petersen CP. tec-1 kinase negatively regulates regenerative neurogenesis in planarians. Elife. 2020;9:e47293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kang HJ, Voleti B, Hajszan T, Rajkowska G, Stockmeier CA, Licznerski P, et al. Decreased expression of synapse-related genes and loss of synapses in major depressive disorder. Nat Med. 2012;18:1413–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ito H, Morishita R, Sudo K, Nishimura YV, Inaguma Y, Iwamoto I, et al. Biochemical and morphological characterization of MAGI-1 in neuronal tissue. J Neurosci Res. 2012;90:1776–81.

    Article  CAS  PubMed  Google Scholar 

  54. Chibuk TK, Bischof JM, Wevrick R. A necdin/MAGE-like gene in the chromosome 15 autism susceptibility region: expression, imprinting, and mapping of the human and mouse orthologues. BMC Genet. 2001;2:22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Roll P, Rudolf G, Pereira S, Royer B, Scheffer IE, Massacrier A, et al. SRPX2 mutations in disorders of language cortex and cognition. Proc Natl Acad Sci USA. 2006;15:1195–207.

    CAS  Google Scholar 

  56. Takagi M, Absalon MJ, McLure KG, Kastan MB. Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin. Cell. 2005;123:49–63.

    Article  CAS  PubMed  Google Scholar 

  57. Mazan-Mamczarz K, Galbán S, López de Silanes I, Martindale JL, Atasoy U, Keene JD, et al. RNA-binding protein HuR enhances p53 translation in response to ultraviolet light irradiation. Proc Natl Acad Sci USA. 2003;100:8354–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhang J, Cho SJ, Shu L, Yan W, Guerrero T, Kent M, et al. Translational repression of p53 by RNPC1, a p53 target overexpressed in lymphomas. Genes Dev. 2011;25:1528–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Nosyreva E, Kavalali ET. Activity-dependent augmentation of spontaneous neurotransmission during endoplasmic reticulum stress. J Neurosci. 2010;30:7358–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lahr RM, Fonseca BD, Ciotti GE, Al-Ashtal HA, Jia JJ, Niklaus MR, et al. La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs. eLife. 2017;6:e24146.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Ogami K, Oishi Y, Sakamoto K, Okumura M, Yamagishi R, Inoue T, et al. mTOR- and LARP1-dependent regulation of TOP mRNA poly(A) tail and ribosome loading. Cell Rep. 2022;41:111548.

    Article  CAS  PubMed  Google Scholar 

  62. Gentilella A, Morón-Duran FD, Fuentes P, Zweig-Rocha G, Riaño-Canalias F, Pelletier J, et al. Autogenous control of 5′TOP mRNA stability by 40S Ribosomes. Mol Cell. 2017;67:55–70.e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Sun W, Laubach K, Lucchessi C, Zhang Y, Chen M, Zhang J, et al. Fine-tuning p53 activity by modulating the interaction between eukaryotic translation initiation factor eIF4E and RNA-binding protein RBM38. Genes Dev. 2021;35:542–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Delbridge ARD, Kueh AJ, Ke F, Zamudio NM, El-Saafin F, Jansz N, et al. Loss of p53 causes stochastic aberrant X-Chromosome inactivation and female-specific neural tube defects. Cell Rep. 2019;27:442–54.e5.

    Article  CAS  PubMed  Google Scholar 

  65. LaRese TP, Rheaume BA, Abraham R, Eipper BA, Mains RE. Sex-specific gene expression in the mouse nucleus accumbens before and after cocaine exposure. J Endoc Soc. 2019;3:468–87.

    Article  CAS  Google Scholar 

  66. Feng Z, Hu W, Teresky AK, Hernando E, Cordon-Cardo C, Levine AJ. Declining p53 function in the aging process: a possible mechanism for the increased tumor incidence in older populations. Proc Natl Acad Sci USA. 2007;104:16633–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Berger C, Qian Y, Chen X. The p53-estrogen receptor loop in cancer. Curr Mol Med. 2013;13:1229–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work is supported by National Institute of Health R01NS105615, R01MH124827 and R21MH122840 to N-P.T.

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Authors and Affiliations

  1. Department of Molecular and Integrative Physiology, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Kwan Young Lee, Yeeun Yook, Catherine A. Christian-Hinman & Nien-Pei Tsai

  2. School of Information Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Haohan Wang

  3. Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Justin S. Rhodes, Catherine A. Christian-Hinman & Nien-Pei Tsai

  4. Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Justin S. Rhodes, Catherine A. Christian-Hinman & Nien-Pei Tsai

  5. Department of Psychology, University of Illinois at Urbana-Champaign, Champaign, IL, 61820, USA

    Justin S. Rhodes

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KYL and NPT designed the research. KYL, HW and YY performed the research and analyzed the data. CAC-H and JSR provided essential instrumental support. KYL and NPT wrote the manuscript.

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Lee, K.Y., Wang, H., Yook, Y. et al. Tumor suppressor p53 modulates activity-dependent synapse strengthening, autism-like behavior and hippocampus-dependent learning. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02268-9

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