A biomarker-authenticated model of schizophrenia implicating NPTX2 loss of function

Schizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that builds on our observation that the synaptic immediate early gene NPTX2 is reduced in cerebrospinal fluid of individuals with recent onset sch...

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Published inScience advances Vol. 7; no. 48; p. eabf6935
Main Authors Xiao, Mei-Fang, Roh, Seung-Eon, Zhou, Jiechao, Chien, Chun-Che, Lucey, Brendan P, Craig, Michael T, Hayes, Lindsay N, Coughlin, Jennifer M, Leweke, F Markus, Jia, Min, Xu, Desheng, Zhou, Weiqiang, Conover Talbot, Jr, C, Arnold, Don B, Staley, Melissa, Jiang, Cindy, Reti, Irving M, Sawa, Akira, Pelkey, Kenneth A, McBain, Chris J, Savonenko, Alena, Worley, Paul F
Format Journal Article
LanguageEnglish
Published United States American Association for the Advancement of Science 26.11.2021
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Diseases and Disorders
Neuroscience
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Abstract Schizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that builds on our observation that the synaptic immediate early gene NPTX2 is reduced in cerebrospinal fluid of individuals with recent onset schizophrenia. NPTX2 plays an essential role in maintaining excitatory homeostasis by adaptively enhancing circuit inhibition. NPTX2 function requires activity-dependent exocytosis and dynamic shedding at synapses and is coupled to circadian behavior. Behavior-linked NPTX2 trafficking is abolished by mutations that disrupt select activity-dependent plasticity mechanisms of excitatory neurons. Modeling NPTX2 loss of function results in failure of parvalbumin interneurons in their adaptive contribution to behavioral stress, and animals exhibit multiple neuropsychiatric domains. Because the genetics of schizophrenia encompasses diverse proteins that contribute to excitatory synapse plasticity, the identified vulnerability of NPTX2 function can provide a framework for assessing the impact of genetics and the intersection with stress.
AbstractList CSF NPTX2 is a biomarker of schizophrenia and supports a model that integrates across genetics, pharmacology, and behavior. Schizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that builds on our observation that the synaptic immediate early gene NPTX2 is reduced in cerebrospinal fluid of individuals with recent onset schizophrenia. NPTX2 plays an essential role in maintaining excitatory homeostasis by adaptively enhancing circuit inhibition. NPTX2 function requires activity-dependent exocytosis and dynamic shedding at synapses and is coupled to circadian behavior. Behavior-linked NPTX2 trafficking is abolished by mutations that disrupt select activity-dependent plasticity mechanisms of excitatory neurons. Modeling NPTX2 loss of function results in failure of parvalbumin interneurons in their adaptive contribution to behavioral stress, and animals exhibit multiple neuropsychiatric domains. Because the genetics of schizophrenia encompasses diverse proteins that contribute to excitatory synapse plasticity, the identified vulnerability of NPTX2 function can provide a framework for assessing the impact of genetics and the intersection with stress.
Schizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that builds on our observation that the synaptic immediate early gene NPTX2 is reduced in cerebrospinal fluid of individuals with recent onset schizophrenia. NPTX2 plays an essential role in maintaining excitatory homeostasis by adaptively enhancing circuit inhibition. NPTX2 function requires activity-dependent exocytosis and dynamic shedding at synapses and is coupled to circadian behavior. Behavior-linked NPTX2 trafficking is abolished by mutations that disrupt select activity-dependent plasticity mechanisms of excitatory neurons. Modeling NPTX2 loss of function results in failure of parvalbumin interneurons in their adaptive contribution to behavioral stress, and animals exhibit multiple neuropsychiatric domains. Because the genetics of schizophrenia encompasses diverse proteins that contribute to excitatory synapse plasticity, the identified vulnerability of NPTX2 function can provide a framework for assessing the impact of genetics and the intersection with stress.
Author Craig, Michael T
McBain, Chris J
Savonenko, Alena
Conover Talbot, Jr, C
Jiang, Cindy
Lucey, Brendan P
Leweke, F Markus
Zhou, Jiechao
Staley, Melissa
Xu, Desheng
Roh, Seung-Eon
Sawa, Akira
Worley, Paul F
Zhou, Weiqiang
Pelkey, Kenneth A
Coughlin, Jennifer M
Arnold, Don B
Reti, Irving M
Xiao, Mei-Fang
Jia, Min
Chien, Chun-Che
Hayes, Lindsay N
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Cites_doi 10.1016/j.neuron.2015.05.022
10.1016/S0140-6736(15)01121-6
10.1016/j.neuron.2010.11.008
10.1016/j.neuron.2013.05.016
10.1016/S0896-6273(03)00463-X
10.1126/science.aai8355
10.1523/JNEUROSCI.0167-14.2014
10.1016/j.biopsych.2017.06.033
10.1126/science.aah5982
10.1038/nature12929
10.1038/35082096
10.1523/JNEUROSCI.17-08-02876.1997
10.1016/j.neuron.2008.05.023
10.1155/2019/6804575
10.1016/j.schres.2016.10.040
10.1016/j.neuron.2013.04.017
10.1016/j.psychres.2018.04.036
10.1371/journal.pone.0076478
10.1038/mp.2013.38
10.1016/j.schres.2007.04.025
10.1038/nrn.2017.125
10.1001/jamapsychiatry.2015.0533
10.1016/j.neuron.2013.08.038
10.1101/lm.028621.112
10.1016/j.cell.2013.07.001
10.1073/pnas.0907143106
10.1016/j.celrep.2016.07.044
10.1016/j.cell.2011.09.036
10.1176/ajp.103.3.309
10.1192/bjp.bp.111.096321
10.1038/npjschz.2016.3
10.1016/j.neuron.2019.08.031
10.1155/2016/6212983
10.1093/schbul/sbs076
10.1002/ana.25702
10.1038/nature16549
10.1016/S0896-6273(00)80782-5
10.1038/nbt.3122
10.1002/ana.25117
10.1016/j.molcel.2019.05.004
10.1038/nn.2621
10.1093/hmg/ddw019
10.1186/1750-1326-8-18
10.1038/s41467-017-01752-5
10.1093/nar/gkv007
10.1016/j.neuron.2006.08.034
10.1038/nn2035
10.1093/schbul/sbs010
10.7554/eLife.23798
10.1371/journal.pone.0138127
10.1038/nature13595
10.1038/nmeth.3317
10.1177/0269881119845820
10.1098/rstb.2016.0158
10.1016/j.neuron.2015.02.020
10.1016/j.neuron.2013.10.002
10.1073/pnas.2105388118
10.1126/science.aav2546
10.1016/j.neuron.2015.03.030
10.1093/schbul/sbp006
10.1016/j.neuron.2008.01.010
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References e_1_3_3_50_2
Van’t Spijker H. M. (e_1_3_3_36_2) 2019; 2019
e_1_3_3_16_2
Parslow A. (e_1_3_3_58_2) 2014
e_1_3_3_18_2
e_1_3_3_39_2
e_1_3_3_12_2
e_1_3_3_37_2
e_1_3_3_14_2
e_1_3_3_35_2
e_1_3_3_56_2
e_1_3_3_33_2
e_1_3_3_54_2
e_1_3_3_10_2
e_1_3_3_31_2
e_1_3_3_52_2
e_1_3_3_40_2
e_1_3_3_61_2
e_1_3_3_5_2
e_1_3_3_7_2
e_1_3_3_9_2
e_1_3_3_27_2
e_1_3_3_29_2
e_1_3_3_23_2
e_1_3_3_48_2
e_1_3_3_25_2
e_1_3_3_46_2
e_1_3_3_44_2
e_1_3_3_3_2
e_1_3_3_21_2
e_1_3_3_42_2
e_1_3_3_63_2
e_1_3_3_51_2
e_1_3_3_17_2
e_1_3_3_19_2
e_1_3_3_38_2
e_1_3_3_13_2
e_1_3_3_59_2
e_1_3_3_15_2
e_1_3_3_34_2
e_1_3_3_57_2
e_1_3_3_32_2
e_1_3_3_55_2
e_1_3_3_11_2
e_1_3_3_30_2
e_1_3_3_53_2
e_1_3_3_62_2
e_1_3_3_60_2
e_1_3_3_6_2
e_1_3_3_8_2
e_1_3_3_28_2
e_1_3_3_49_2
e_1_3_3_24_2
e_1_3_3_47_2
e_1_3_3_26_2
e_1_3_3_45_2
e_1_3_3_2_2
e_1_3_3_20_2
e_1_3_3_43_2
e_1_3_3_4_2
e_1_3_3_22_2
e_1_3_3_41_2
References_xml – ident: e_1_3_3_19_2
  doi: 10.1016/j.neuron.2015.05.022
– ident: e_1_3_3_2_2
  doi: 10.1016/S0140-6736(15)01121-6
– ident: e_1_3_3_21_2
  doi: 10.1016/j.neuron.2010.11.008
– ident: e_1_3_3_25_2
  doi: 10.1016/j.neuron.2013.05.016
– ident: e_1_3_3_28_2
  doi: 10.1016/S0896-6273(03)00463-X
– ident: e_1_3_3_22_2
  doi: 10.1126/science.aai8355
– ident: e_1_3_3_18_2
  doi: 10.1523/JNEUROSCI.0167-14.2014
– ident: e_1_3_3_6_2
  doi: 10.1016/j.biopsych.2017.06.033
– ident: e_1_3_3_44_2
  doi: 10.1126/science.aah5982
– ident: e_1_3_3_4_2
  doi: 10.1038/nature12929
– ident: e_1_3_3_20_2
  doi: 10.1038/35082096
– ident: e_1_3_3_13_2
  doi: 10.1523/JNEUROSCI.17-08-02876.1997
– ident: e_1_3_3_17_2
  doi: 10.1016/j.neuron.2008.05.023
– volume: 2019
  start-page: 6804575
  year: 2019
  ident: e_1_3_3_36_2
  article-title: Neuronal pentraxin 2 binds PNNs and enhances PNN formation
  publication-title: Neural Plast.
  doi: 10.1155/2019/6804575
  contributor:
    fullname: Van’t Spijker H. M.
– ident: e_1_3_3_32_2
  doi: 10.1016/j.schres.2016.10.040
– ident: e_1_3_3_35_2
  doi: 10.1016/j.neuron.2013.04.017
– ident: e_1_3_3_12_2
  doi: 10.1016/j.psychres.2018.04.036
– ident: e_1_3_3_57_2
  doi: 10.1371/journal.pone.0076478
– ident: e_1_3_3_50_2
  doi: 10.1038/mp.2013.38
– ident: e_1_3_3_33_2
  doi: 10.1016/j.schres.2007.04.025
– ident: e_1_3_3_8_2
  doi: 10.1038/nrn.2017.125
– ident: e_1_3_3_34_2
  doi: 10.1001/jamapsychiatry.2015.0533
– start-page: 51086
  year: 2014
  ident: e_1_3_3_58_2
  article-title: Sample drift correction following 4D confocal time-lapse imaging
  publication-title: J. Vis. Exp.
  contributor:
    fullname: Parslow A.
– ident: e_1_3_3_42_2
  doi: 10.1016/j.neuron.2013.08.038
– ident: e_1_3_3_46_2
  doi: 10.1101/lm.028621.112
– ident: e_1_3_3_23_2
  doi: 10.1016/j.cell.2013.07.001
– ident: e_1_3_3_60_2
  doi: 10.1073/pnas.0907143106
– ident: e_1_3_3_45_2
  doi: 10.1016/j.celrep.2016.07.044
– ident: e_1_3_3_54_2
  doi: 10.1016/j.cell.2011.09.036
– ident: e_1_3_3_3_2
  doi: 10.1176/ajp.103.3.309
– ident: e_1_3_3_53_2
  doi: 10.1192/bjp.bp.111.096321
– ident: e_1_3_3_56_2
  doi: 10.1038/npjschz.2016.3
– ident: e_1_3_3_52_2
  doi: 10.1016/j.neuron.2019.08.031
– ident: e_1_3_3_48_2
  doi: 10.1155/2016/6212983
– ident: e_1_3_3_11_2
  doi: 10.1093/schbul/sbs076
– ident: e_1_3_3_41_2
  doi: 10.1002/ana.25702
– ident: e_1_3_3_7_2
  doi: 10.1038/nature16549
– ident: e_1_3_3_27_2
  doi: 10.1016/S0896-6273(00)80782-5
– ident: e_1_3_3_62_2
  doi: 10.1038/nbt.3122
– ident: e_1_3_3_39_2
  doi: 10.1002/ana.25117
– ident: e_1_3_3_15_2
  doi: 10.1016/j.molcel.2019.05.004
– ident: e_1_3_3_24_2
  doi: 10.1038/nn.2621
– ident: e_1_3_3_47_2
  doi: 10.1093/hmg/ddw019
– ident: e_1_3_3_59_2
  doi: 10.1186/1750-1326-8-18
– ident: e_1_3_3_31_2
  doi: 10.1038/s41467-017-01752-5
– ident: e_1_3_3_63_2
  doi: 10.1093/nar/gkv007
– ident: e_1_3_3_16_2
  doi: 10.1016/j.neuron.2006.08.034
– ident: e_1_3_3_43_2
  doi: 10.1038/nn2035
– ident: e_1_3_3_9_2
  doi: 10.1093/schbul/sbs010
– ident: e_1_3_3_30_2
  doi: 10.7554/eLife.23798
– ident: e_1_3_3_37_2
  doi: 10.1371/journal.pone.0138127
– ident: e_1_3_3_5_2
  doi: 10.1038/nature13595
– ident: e_1_3_3_61_2
  doi: 10.1038/nmeth.3317
– ident: e_1_3_3_51_2
  doi: 10.1177/0269881119845820
– ident: e_1_3_3_55_2
  doi: 10.1098/rstb.2016.0158
– ident: e_1_3_3_26_2
  doi: 10.1016/j.neuron.2015.02.020
– ident: e_1_3_3_49_2
  doi: 10.1016/j.neuron.2013.10.002
– ident: e_1_3_3_38_2
  doi: 10.1073/pnas.2105388118
– ident: e_1_3_3_40_2
  doi: 10.1126/science.aav2546
– ident: e_1_3_3_14_2
  doi: 10.1016/j.neuron.2015.03.030
– ident: e_1_3_3_10_2
  doi: 10.1093/schbul/sbp006
– ident: e_1_3_3_29_2
  doi: 10.1016/j.neuron.2008.01.010
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Snippet Schizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that...
CSF NPTX2 is a biomarker of schizophrenia and supports a model that integrates across genetics, pharmacology, and behavior. Schizophrenia is a polygenetic...
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Neuroscience
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Title A biomarker-authenticated model of schizophrenia implicating NPTX2 loss of function
URI https://www.ncbi.nlm.nih.gov/pubmed/34818031
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https://pubmed.ncbi.nlm.nih.gov/PMC8612534
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