Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice.
ASD
Anxiety
Learning
Medial prefrontal cortex
Memory
Protein tyrosine phosphatase receptor delta
Synaptic transmission
Journal
Biological research
ISSN: 0717-6287
Titre abrégé: Biol Res
Pays: England
ID NLM: 9308271
Informations de publication
Date de publication:
18 Jun 2024
18 Jun 2024
Historique:
received:
07
03
2024
accepted:
07
06
2024
medline:
19
6
2024
pubmed:
19
6
2024
entrez:
18
6
2024
Statut:
epublish
Résumé
The brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRβ in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown. Here, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety. These results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.
Sections du résumé
BACKGROUND
BACKGROUND
The brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRβ in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown.
RESULTS
RESULTS
Here, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety.
CONCLUSIONS
CONCLUSIONS
These results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.
Identifiants
pubmed: 38890753
doi: 10.1186/s40659-024-00522-0
pii: 10.1186/s40659-024-00522-0
doi:
Substances chimiques
Receptor-Like Protein Tyrosine Phosphatases, Class 2
EC 3.1.3.48
Ptprd protein, mouse
EC 3.1.3.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
40Subventions
Organisme : Agencia Nacional de Investigación y Desarrollo
ID : 1201848
Organisme : Agencia Nacional de Investigación y Desarrollo
ID : 1210507
Organisme : Agencia Nacional de Investigación y Desarrollo
ID : 1231012
Organisme : Agencia Nacional de Investigación y Desarrollo
ID : 11220708
Organisme : Agencia Nacional de Investigación y Desarrollo
ID : 3190793
Organisme : Agencia Nacional de Investigación y Desarrollo
ID : EQM160154
Organisme : Agencia Nacional de Investigación y Desarrollo
ID : 21201603
Organisme : CIHR
ID : Canadian Institutes of Health Research
Pays : Canada
Informations de copyright
© 2024. The Author(s).
Références
Lodato S, Arlotta P. Generating neuronal diversity in the mammalian cerebral cortex. Annu Rev Cell Dev Biol. 2015;31:699–720.
pubmed: 26359774
pmcid: 4778709
doi: 10.1146/annurev-cellbio-100814-125353
Lim L, Llorca A, Marín O. Development and functional diversification of Cortical Interneurons. Neuron. 2018;100(2):294–313.
pubmed: 30359598
pmcid: 6290988
doi: 10.1016/j.neuron.2018.10.009
Matho KS, Huilgol D, Galbavy W, He M, Kim G, An X, et al. Genetic dissection of the glutamatergic neuron system in cerebral cortex. Nature. 2021;598(7879):182–7.
pubmed: 34616069
pmcid: 8494647
doi: 10.1038/s41586-021-03955-9
Sohal VS, Rubenstein JLR. Excitation-inhibition balance as a framework for investigating mechanisms in neuropsychiatric disorders. Mol Psychiatry. 2019;24(9):1248–57.
pubmed: 31089192
pmcid: 6742424
doi: 10.1038/s41380-019-0426-0
Juric-Sekhar G, Hevner RF. Malformations of cerebral cortex development: molecules and mechanisms. Annu Rev Pathol. 2019;14:293–318.
pubmed: 30677308
pmcid: 6938687
doi: 10.1146/annurev-pathmechdis-012418-012927
Courchesne E, Gazestani VH, Lewis NE. Prenatal origins of ASD- the when, what, and how of ASD Development. Trends Neurosci. 2020;43(5):326–42.
pubmed: 32353336
pmcid: 7373219
doi: 10.1016/j.tins.2020.03.005
Zamanpoor M. Schizophrenia in a genomic era: a review from the pathogenesis, genetic and environmental etiology to diagnosis and treatment insights. Psychiatr Genet. 2019;30(1):1–9.
doi: 10.1097/YPG.0000000000000245
Faraone SV, Larsson H. Genetics of attention deficit hyperactivity disorder. Mol Psychiatry. 2018;24(4):562–75.
pubmed: 29892054
pmcid: 6477889
doi: 10.1038/s41380-018-0070-0
Bowling KM, Thompson ML, Amaral MD, Finnila CR, Hiatt SM, Engel KL, et al. Genomic diagnosis for children with intellectual disability and / or developmental delay. Genome Med. 2017;9(1):43.
pubmed: 28554332
pmcid: 5448144
doi: 10.1186/s13073-017-0433-1
Gazzellone MJ, Zarrei M, Burton CL, Walker S, Uddin M, Shaheen SM, et al. Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation. J Neurodev Disord. 2016;8(36):1–11.
Tomita H, Cornejo F, Kaplan DR, Miller FD, Cancino GI, Woodard CL, et al. The Protein Tyrosine Phosphatase Receptor Delta regulates Developmental Neurogenesis Article the protein tyrosine phosphatase receptor Delta regulates Developmental Neurogenesis. Cell Rep. 2020;30(1):215–28.
pubmed: 31914388
doi: 10.1016/j.celrep.2019.11.033
Cornejo F, Franchini N, Cortés BI, Elgueta D, Cancino GI. Neural conditional ablation of the protein tyrosine phosphatase receptor Delta PTPRD impairs gliogenesis in the developing mouse brain cortex. Front Cell Dev Biol. 2024;12:1357862.
pubmed: 38487272
pmcid: 10937347
doi: 10.3389/fcell.2024.1357862
Pulido R, Serra-Pagès C, Tang M, Streuli M. The LAR/PTP delta/PTP sigma subfamily of transmembrane protein-tyrosine-phosphatases: multiple human LAR, PTP delta, and PTP Sigma isoforms are expressed in a tissue-specific manner and associate with the LAR-interacting protein LIP.1. Proc Natl Acad Sci U S A. 1995;92(25):11686–90.
pubmed: 8524829
pmcid: 40467
doi: 10.1073/pnas.92.25.11686
Cornejo F, Cortés BI, Findlay GM, Cancino GI. LAR Receptor Tyrosine Phosphatase Family in healthy and diseased brain. Front Cell Dev Biol. 2021;9:659951.
pubmed: 34966732
pmcid: 8711739
doi: 10.3389/fcell.2021.659951
Takahashi H, Craig AM. Protein tyrosine phosphatases PTP D, PTP s, and LAR : presynaptic hubs for synapse organization. Trends Neurosci. 2013;36(9):522–34.
pubmed: 23835198
pmcid: 3789601
doi: 10.1016/j.tins.2013.06.002
Han KA, Ko JS, Pramanik G, Kim JY, Tabuchi K. PTPσ drives excitatory presynaptic assembly via various extracellular and intracellular mechanisms. J Neurosci. 2018;18:6700–21.
doi: 10.1523/JNEUROSCI.0672-18.2018
Park H, Choi Y, Jung H, Kim S, Lee S, Han H, et al. Splice-dependent trans-synaptic PTP d – IL 1 RAPL 1 interaction regulates synapse formation and non-REM sleep. EMBO J. 2020;39(11):e104150.
pubmed: 32347567
pmcid: 7265247
doi: 10.15252/embj.2019104150
Sclip A, Südhof TC. LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses. Elife. 2020;9:e53406.
pubmed: 31985401
pmcid: 6984820
doi: 10.7554/eLife.53406
Han KA, Lee HY, Lim D, Shin J, Yoon TH, Liu X, et al. Receptor protein tyrosine phosphatase delta is not essential for synapse maintenance or transmission at hippocampal synapses. Mol Brain. 2020;13(1):94.
pubmed: 32552840
pmcid: 7301452
doi: 10.1186/s13041-020-00629-x
Cancino GI, Fatt MP, Miller FD, Kaplan DR. Conditional ablation of p63 indicates that it is essential for embryonic development of the central nervous system. Cell Cycle. 2015;14(20):3270–81.
pubmed: 26359534
pmcid: 4825551
doi: 10.1080/15384101.2015.1087618
George P, Keith F. In. The mouse brain in Stereotaxis coordinates. 2004. p. 71–5.
Delgado-Acevedo C, Estay SF, Radke AK, Sengupta A, Escobar AP, Henríquez-Belmar F, et al. Behavioral and synaptic alterations relevant to obsessive-compulsive disorder in mice with increased EAAT3 expression. Neuropsychopharmacology. 2019;44(6):1163–73.
pubmed: 30622300
doi: 10.1038/s41386-018-0302-7
Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2006;1(2):848–58.
pubmed: 17406317
pmcid: 2895266
doi: 10.1038/nprot.2006.116
Kraeuter AK, Guest PC, Sarnyai Z. The Y-Maze for Assessment of spatial working and reference memory in mice. Methods Mol Biol. 2019;1916:105–11.
pubmed: 30535688
doi: 10.1007/978-1-4939-8994-2_10
Yang G, Cancino GI, Zahr SK, Guskjolen A, Voronova A, Gallagher D, et al. A Glo1-Methylglyoxal pathway that is perturbed in maternal diabetes regulates embryonic and adult neural stem cell pools in murine offspring. Cell Rep. 2016;17(4):1022–36.
pubmed: 27760310
doi: 10.1016/j.celrep.2016.09.067
Kraeuter AK, Guest PC, Sarnyai Z. The elevated plus maze test for measuring anxiety-like Behavior in rodents. Methods Mol Biol. 2019;1916:69–74.
pubmed: 30535682
doi: 10.1007/978-1-4939-8994-2_4
Gallagher D, Voronova A, Zander MA, Cancino GI, Bramall A, Krause MP, et al. Article Ankrd11 is a chromatin Regulator involved in Autism that is essential for neural development. Dev Cell. 2015;32(1):31–42.
pubmed: 25556659
doi: 10.1016/j.devcel.2014.11.031
Moya PR, Fox MA, Jensen CL, Laporte JL, French HT, Wendland JR, et al. Altered 5-HT2C receptor agonist-induced responses and 5-HT2C receptor RNA editing in the amygdala of serotonin transporter knockout mice. BMC Pharmacol. 2011;11:3.
pubmed: 21473759
pmcid: 3080299
doi: 10.1186/1471-2210-11-3
Anastasiades PG, Carter AG. Circuit organization of the rodent medial prefrontal cortex. Trends Neurosci. 2021;44(7):550–63.
pubmed: 33972100
pmcid: 8222144
doi: 10.1016/j.tins.2021.03.006
Pittaras EC, Faure A, Leray X, Moraitopoulou E, Cressant A, Rabat AA, et al. Neuronal nicotinic receptors are crucial for tuning of E/I balance in Prelimbic Cortex and for decision-making processes. Front Psychiatry. 2016;7:171.
pubmed: 27790159
pmcid: 5064178
doi: 10.3389/fpsyt.2016.00171
Angenstein F, Niessen HG, Goldschmidt J, Lison H, Altrock WD, Gundelfinger ED, et al. Manganese-enhanced MRI reveals structural and functional changes in the cortex of Bassoon mutant mice. Cereb Cortex. 2007;17(1):28–36.
pubmed: 16452644
doi: 10.1093/cercor/bhj121
Perrenoud Q, Rossier J, Férézou I, Geoffroy H, Gallopin T, Vitalis T, et al. Activation of cortical 5-HT(3) receptor-expressing interneurons induces NO mediated vasodilatations and NPY mediated vasoconstrictions. Front Neural Circuits. 2012;6:50.
pubmed: 22907992
pmcid: 3415676
doi: 10.3389/fncir.2012.00050
Fang WQ, Chen WW, Jiang L, Liu K, Yung WH, Fu AKY, et al. Overproduction of Upper-Layer neurons in the Neocortex leads to autism-like features in mice. Cell Rep. 2014;9(5):1635–43.
pubmed: 25466248
doi: 10.1016/j.celrep.2014.11.003
Sahin M, Dowling JJ, Hockfield S. Seven protein tyrosine phosphatases are differentially expressed in the developing rat brain. J Comp Neurol. 1995;351(4):617–31.
pubmed: 7721987
doi: 10.1002/cne.903510410
Takahashi H, Katayama K, Sohya K, Miyamoto H, Prasad T, Matsumoto Y, et al. Selective control of inhibitory synapse development by Slitrk3-PTP d trans-synaptic interaction. Nat Neurosci. 2012;15(3):389–98.
pubmed: 22286174
pmcid: 3288805
doi: 10.1038/nn.3040
Yoshida T, Yamagata A, Imai A, Kim J, Izumi I, Mishina M, et al. Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice. Nat Commun. 2021;12(1):1848.
pubmed: 33758193
pmcid: 7988105
doi: 10.1038/s41467-021-22059-6
Yim YS, Kwon Y, Nam J, In H, Lee K, Goo D et al. Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases. Proceedings of the National Academy of Sciences. 2013;110:4057–62.
Li W, Chen R, Feng L, Dang X, Liu J, Chen T, et al. Genome-wide meta-analysis, functional genomics and integrative analyses implicate new risk genes and therapeutic targets for anxiety disorders. Nat Hum Behav. 2024;8(2):361–79.
pubmed: 37945807
doi: 10.1038/s41562-023-01746-y
Kraeuter AK, Guest PC, Sarnyai Z. The Open Field Test for measuring locomotor activity and Anxiety-like Behavior. Methods Mol Biol. 2019;1916:99–103.
pubmed: 30535687
doi: 10.1007/978-1-4939-8994-2_9
Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, et al. Convergence of genes and Cellular pathways Dysregulated in Autism Spectrum disorders. Am J Hum Genet. 2014;94(5):677–94.
pubmed: 24768552
pmcid: 4067558
doi: 10.1016/j.ajhg.2014.03.018
Levy D, Ronemus M, Yamrom B, Leotta A, Kendall J, Marks S, et al. Rare De Novo and Transmitted Copy-number variation in autistic Spectrum disorders. Neuron. 2011;70(5):886–97.
pubmed: 21658582
doi: 10.1016/j.neuron.2011.05.015
Gai X, Xie HM, Perin JC, Takahashi N, Murphy K, Wenocur AS, et al. Rare structural variation of synapse and neurotransmission genes in autism. Mol Psychiatry. 2011;17(14):402–11.
pubmed: 21358714
pmcid: 3314176
Liu X, Shimada T, Otowa T, Wu YY, Kawamura Y, Tochigi M, et al. Genome-Wide Association Study of Autism Spectrum Disorder in the east Asian populations. Autism Res. 2016;9(3):340–9.
pubmed: 26314684
doi: 10.1002/aur.1536
Moy SS, Nadler JJ, Perez A. Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes Brain Behav. 2004;3(4):287–302.
pubmed: 15344922
doi: 10.1111/j.1601-1848.2004.00076.x
Kalueff AV, Aldridge JW, Laporte JL, Murphy DL, Tuohimaa P. Analyzing grooming microstructure in neurobehavioral experiments. Nat Protoc. 2007;2(10):2538–44.
pubmed: 17947996
doi: 10.1038/nprot.2007.367
Gandhi T, Lee CC. Neural mechanisms underlying repetitive behaviors in Rodent models of Autism Spectrum disorders. Front Cell Neurosci. 2021;14(59):1–44.
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(2):361–73.
pubmed: 19189082
pmcid: 2899706
doi: 10.1007/s00213-009-1466-y
Packer A. Neocortical neurogenesis and the etiology of Autism Spectrum Disorder. Neurosci Biobehav Rev. 2016;64:185–95.
pubmed: 26949225
doi: 10.1016/j.neubiorev.2016.03.002
Chen JA, Peñagarikano O, Belgard TG, Swarup V, Geschwind DH. The emerging picture of Autism Spectrum Disorder: Genetics and Pathology. Annu Rev Pathol. 2015;10:111–44.
pubmed: 25621659
doi: 10.1146/annurev-pathol-012414-040405
Ho EV, Welch A, Thompson SL, Knowles JA, Dulawa SC. Mice lacking Ptprd exhibit deficits in goal- directed behavior and female-specific impairments in sensorimotor gating. PLoS ONE. 2023;18(5):e0277446.
pubmed: 37205689
pmcid: 10198499
doi: 10.1371/journal.pone.0277446
Uetani N, Kato K, Ogura H, Mizuno K, Kawano K, Mikoshiba K, et al. Impaired learning with enhanced hippocampal long-term potentiation in PTPδ-deficient mice. EMBO J. 2000;19(12):2775–85.
pubmed: 10856223
pmcid: 203365
doi: 10.1093/emboj/19.12.2775
Drgonova J, Walther D, Wang KJ, Hartstein GL, Lochte B, Troncoso J. Mouse model for protein tyrosine phosphatase D (PTPRD) associations with restless Leg syndrome or Willis-Ekbom Disease and Addiction: reduced expression alters Locomotion, Sleep behaviors and Cocaine-conditioned place preference. Mol Med. 2015;21(1):717–25.
pubmed: 26181631
pmcid: 4749486
doi: 10.2119/molmed.2015.00017
Casanova MF. Autism as a sequence: from heterochronic germinal cell divisions to abnormalities of cell migration and cortical dysplasias. Med Hypotheses. 2014;83(1):32–8. 2014/04/13.
pubmed: 24780284
pmcid: 4070182
doi: 10.1016/j.mehy.2014.04.014
Lee E, Lee J, Kim E. Excitation / inhibition imbalance in animal models of Autism Spectrum disorders. Biol Psychiatry. 2017;81(10):838–47.
pubmed: 27450033
doi: 10.1016/j.biopsych.2016.05.011
Takumi T, Tamada K, Hatanaka F, Nakai N, Bolton PF. Behavioral neuroscience of autism. Neurosci Biobehav Rev. 2019;110:60–76.
pubmed: 31059731
doi: 10.1016/j.neubiorev.2019.04.012