S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
05 11 2021
05 11 2021
Historique:
received:
14
06
2021
accepted:
21
10
2021
revised:
19
10
2021
entrez:
6
11
2021
pubmed:
7
11
2021
medline:
1
2
2022
Statut:
epublish
Résumé
Autism Spectrum Disorders (ASD) are caused by a combination of genetic predisposition and nongenetic factors. Among the nongenetic factors, maternal immune system activation and zinc deficiency have been proposed. Intriguingly, as a genetic factor, copy-number variations in S100B, a pro-inflammatory damage-associated molecular pattern (DAMP), have been associated with ASD, and increased serum S100B has been found in ASD. Interestingly, it has been shown that increased S100B levels affect zinc homeostasis in vitro. Thus, here, we investigated the influence of increased S100B levels in vitro and in vivo during pregnancy in mice regarding zinc availability, the zinc-sensitive SHANK protein networks associated with ASD, and behavioral outcomes. We observed that S100B affects the synaptic SHANK2 and SHANK3 levels in a zinc-dependent manner, especially early in neuronal development. Animals exposed to high S100B levels in utero similarly show reduced levels of free zinc and SHANK2 in the brain. On the behavioral level, these mice display hyperactivity, increased stereotypic and abnormal social behaviors, and cognitive impairment. Pro-inflammatory factors and zinc-signaling alterations converge on the synaptic level revealing a common pathomechanism that may mechanistically explain a large share of ASD cases.
Identifiants
pubmed: 34741005
doi: 10.1038/s41398-021-01694-z
pii: 10.1038/s41398-021-01694-z
pmc: PMC8571423
doi:
Substances chimiques
Microfilament Proteins
0
Nerve Tissue Proteins
0
S100 Calcium Binding Protein beta Subunit
0
S100b protein, mouse
0
Shank2 protein, mouse
0
Shank3 protein, mouse
0
Zinc
J41CSQ7QDS
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
562Informations de copyright
© 2021. The Author(s).
Références
Delorme R, Ey E, Toro R, Leboyer M, Gillberg C, Bourgeron T. Progress toward treatments for synaptic defects in autism. Nat Med. 2013;19:685–94.
pubmed: 23744158
doi: 10.1038/nm.3193
Grabrucker AM. Environmental factors in autism. Front Psychiatry. 2012;3:118.
pubmed: 23346059
Vela G, Stark P, Socha M, Sauer AK, Hagmeyer S, Grabrucker AM. Zinc in gut-brain interaction in autism and neurological disorders. Neural Plast. 2015;2015:972791.
pubmed: 25878905
pmcid: 4386645
doi: 10.1155/2015/972791
Donato R, Cannon BR, Sorci G, Riuzzi F, Hsu K, Weber DJ, et al. Functions of S100 proteins. Curr Mol Med. 2013;13:24–57.
pubmed: 22834835
pmcid: 3707951
doi: 10.2174/156652413804486214
Van Eldik LJ, Griffin WS. S100 beta expression in Alzheimer’s disease: relation to neuropathology in brain regions. Biochim Biophys Acta. 1994;1223:398–403.
pubmed: 7918676
doi: 10.1016/0167-4889(94)90101-5
Peskind ER, Griffin WS, Akama KT, Raskind MA, Van Eldik LJ. Cerebrospinal fluid S100B is elevated in the earlier stages of Alzheimer’s disease. Neurochem Int. 2001;39:409–13.
pubmed: 11578776
doi: 10.1016/S0197-0186(01)00048-1
Süssmuth SD, Tumani H, Ecker D, Ludolph AC. Amyotrophic lateral sclerosis: disease stage related changes of tau protein and S100 beta in cerebrospinal fluid and creatine kinase in serum. Neurosci Lett. 2003;353:57–60.
pubmed: 14642437
doi: 10.1016/j.neulet.2003.09.018
Süssmuth SD, Sperfeld AD, Hinz A, Brettschneider J, Endruhn S, Ludolph AC, et al. CSF glial markers correlate with survival in amyotrophic lateral sclerosis. Neurology. 2010;74:982–87.
pubmed: 20308682
doi: 10.1212/WNL.0b013e3181d5dc3b
Thelin EP, Johannesson L, Nelson D, Bellander BM. S100B is an important outcome predictor in traumatic brain injury. J Neurotrauma. 2013;30:519–28.
pubmed: 23297751
doi: 10.1089/neu.2012.2553
Böhmer AE, Oses JP, Schmidt AP, Perón CS, Krebs CL, Oppitz PP, et al. Neuron-specific enolase, S100B, and glial fibrillary acidic protein levels as outcome predictors in patients with severe traumatic brain injury. Neurosurgery. 2011;68:1624–30. discussion 1630-1631
pubmed: 21368691
doi: 10.1227/NEU.0b013e318214a81f
Egger G, Roetzer KM, Noor A, Lionel AC, Mahmood H, Schwarzbraun T, et al. Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families. Neurogenetics. 2014;15:117–27.
pubmed: 24643514
doi: 10.1007/s10048-014-0394-0
Al-Ayadhi LY, Mostafa GA. A lack of association between elevated serum levels of S100B protein and autoimmunity in autistic children. J Neuroinflammation. 2012;9:54.
pubmed: 22420334
pmcid: 3359166
doi: 10.1186/1742-2094-9-54
Edwards MM, Robinson SR. TNF alpha affects the expression of GFAP and S100B: implications for Alzheimer’s disease. J Neural Transm (Vienna). 2006;113:1709–15.
doi: 10.1007/s00702-006-0479-5
de Souza DF, Leite MC, Quincozes-Santos A, Nardin P, Tortorelli LS, Rigo MM, et al. S100B secretion is stimulated by IL-1beta in glial cultures and hippocampal slices of rats: Likely involvement of MAPK pathway. J Neuroimmunol. 2009;206:52–7.
pubmed: 19042033
doi: 10.1016/j.jneuroim.2008.10.012
de Souza DF, Wartchow K, Hansen F, Lunardi P, Guerra MC, Nardin P, et al. Interleukin-6-induced S100B secretion is inhibited by haloperidol and risperidone. Prog Neuropsychopharmacol Biol Psychiatry. 2013;43:14–22.
pubmed: 23246638
doi: 10.1016/j.pnpbp.2012.12.001
Patterson PH. Maternal infection and immune involvement in autism. Trends Mol Med. 2011;17:389–94.
pubmed: 21482187
pmcid: 3135697
doi: 10.1016/j.molmed.2011.03.001
Hagmeyer S, Cristóvão JS, Mulvihill JJE, Boeckers TM, Gomes CM, Grabrucker AM. Zinc Binding to S100B Affords Regulation of Trace Metal Homeostasis and Excitotoxicity in the Brain. Front Mol Neurosci. 2018;10:456.
pubmed: 29386995
pmcid: 5776125
doi: 10.3389/fnmol.2017.00456
Frederickson CJ, Moncrieff DW. Zinc-containing neurons. Biol Signals. 1994;3:127–39.
pubmed: 7531563
doi: 10.1159/000109536
Frederickson CJ, Bush AI. Synaptically released zinc: physiological functions and pathological effects. Biometals. 2001;14:353–66.
pubmed: 11831465
doi: 10.1023/A:1012934207456
McAllister BB, Dyck RH. Zinc transporter 3 (ZnT3) and vesicular zinc in central nervous system function. Neurosci Biobehav Rev. 2017;80:329–50.
pubmed: 28624432
doi: 10.1016/j.neubiorev.2017.06.006
Takeda A, Suzuki M, Tempaku M, Ohashi K, Tamano H. Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation. Neuroscience. 2015;304:209–16.
pubmed: 26204819
doi: 10.1016/j.neuroscience.2015.07.042
Marger L, Schubert CR, Bertrand D. Zinc: an underappreciated modulatory factor of brain function. Biochem Pharm. 2014;91:426–35.
pubmed: 25130547
doi: 10.1016/j.bcp.2014.08.002
Grabrucker AM. Zinc in the developing brain, in: Moran VH, Lowe N, editors. Nutrition and the developing brain. CRC Press; Baco Raton, FL, USA; 2016. p.143–168.
Grabrucker AM. A role for synaptic zinc in ProSAP/Shank PSD scaffold malformation in autism spectrum disorders. Dev Neurobiol. 2014;74:136–46.
pubmed: 23650259
doi: 10.1002/dneu.22089
Grabrucker AM, Knight MJ, Proepper C, Bockmann J, Joubert M, Rowan M, et al. Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation. EMBO J. 2011;30:569–81.
pubmed: 21217644
pmcid: 3034012
doi: 10.1038/emboj.2010.336
Grabrucker S, Jannetti L, Eckert M, Gaub S, Chhabra R, Pfaender S, et al. Zinc deficiency dysregulates the synaptic ProSAP/Shank scaffold and might contribute to autism spectrum disorders. Brain. 2014;137:137–52.
pubmed: 24277719
doi: 10.1093/brain/awt303
Ghahramani Seno MM, Hu P, Gwadry FG, Pinto D, Marshall CR, Casallo G, et al. Gene and miRNA expression profiles in autism spectrum disorders. Brain Res. 2011;1380:85–97.
pubmed: 20868653
doi: 10.1016/j.brainres.2010.09.046
Leblond CS, Heinrich J, Delorme R, Proepper C, Betancur C, Huguet G, et al. Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. PLoS Genet. 2012;8:e1002521.
pubmed: 22346768
pmcid: 3276563
doi: 10.1371/journal.pgen.1002521
Leblond CS, Nava C, Polge A, Gauthier J, Huguet G, Lumbroso S, et al. Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments. PLoS Genet. 2014;10:e1004580.
pubmed: 25188300
pmcid: 4154644
doi: 10.1371/journal.pgen.1004580
Berkel S, Marshall CR, Weiss B, Howe J, Roeth R, Moog U, et al. Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation. Nat Genet. 2010;42:489–91.
pubmed: 20473310
doi: 10.1038/ng.589
Nemirovsky SI, Córdoba M, Zaiat JJ, Completa SP, Vega PA, González-Morón D, et al. Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder. PLoS ONE. 2015;10:e0116358.
pubmed: 25646853
pmcid: 4315573
doi: 10.1371/journal.pone.0116358
Guo H, Peng Y, Hu Z, Li Y, Xun G, Ou J, et al. Genome-wide copy number variation analysis in a Chinese autism spectrum disorder cohort. Sci Rep. 2017;7:44155.
pubmed: 28281572
pmcid: 5345089
doi: 10.1038/srep44155
Chen CH, Chen HI, Liao HM, Chen YJ, Fang JS, Lee KF, et al. Clinical and molecular characterization of three genomic rearrangements at chromosome 22q13.3 associated with autism spectrum disorder. Psychiatr Genet. 2017;27:23–33.
pubmed: 27846046
doi: 10.1097/YPG.0000000000000151
Bourgeron T. A synaptic trek to autism. Curr Opin Neurobiol. 2009;19:231–34.
pubmed: 19545994
doi: 10.1016/j.conb.2009.06.003
Grabrucker S, Boeckers TM, Grabrucker AM. Gender dependent evaluation of autism like behavior in mice exposed to prenatal zinc deficiency. Front Behav Neurosci. 2016;10:37.
pubmed: 26973485
pmcid: 4776245
doi: 10.3389/fnbeh.2016.00037
Donato R, Heizmann CW. S100B protein in the nervous system and cardiovascular apparatus in normal and pathological conditions. Cardiovasc Psychiatry Neurol. 2010;2010:929712.
pubmed: 21076683
pmcid: 2977937
doi: 10.1155/2010/929712
Sorci G, Agneletti AL, Bianchi R, Donato R. Association of S100B with intermediate filaments and microtubules in glial cells. Biochim Biophys Acta. 1998;1448:277–89.
pubmed: 9920418
doi: 10.1016/S0167-4889(98)00134-7
Ostendorp T, Diez J, Heizmann CW, Fritz G. The crystal structures of human S100B in the zinc- and calcium-loaded state at three pH values reveal zinc ligand swapping. Biochim Biophys Acta. 2011;1813:1083–91.
pubmed: 20950652
doi: 10.1016/j.bbamcr.2010.10.006
Wilder PT, Baldisseri DM, Udan R, Vallely KM, Weber DJ. Location of the Zn(2+)-binding site on S100B as determined by NMR spectroscopy and site-directed mutagenesis. Biochemistry. 2003;42:13410–421.
pubmed: 14621986
doi: 10.1021/bi035334q
Baecker T, Mangus K, Pfaender S, Chhabra R, Boeckers TM, Grabrucker AM. Loss of COMMD1 and copper overload disrupt zinc homeostasis and influence an autism-associated pathway at glutamatergic synapses. Biometals. 2014;27:715–30.
pubmed: 25007851
doi: 10.1007/s10534-014-9764-1
Grabrucker A, Vaida B, Bockmann J, Boeckers TM. Synaptogenesis of hippocampal neurons in primary cell culture. Cell Tissue Res. 2009;338:333–41.
pubmed: 19885679
doi: 10.1007/s00441-009-0881-z
Grabrucker S, Haderspeck JC, Sauer AK, Kittelberger N, Asoglu H, Abaei A, et al. Brain Lateralization in Mice Is Associated with Zinc Signaling and Altered in Prenatal Zinc Deficient Mice That Display Features of Autism Spectrum Disorder. Front Mol Neurosci. 2017;10:450.
pubmed: 29379414
doi: 10.3389/fnmol.2017.00450
Schmeisser MJ, Ey E, Wegener S, Bockmann J, Stempel AV, Kuebler A, et al. Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature. 2012;486:256–60.
pubmed: 22699619
doi: 10.1038/nature11015
Schmeisser MJ. Translational neurobiology in Shank mutant mice–model systems for neuropsychiatric disorders. Ann Anat. 2015;200:115–7.
pubmed: 25917711
doi: 10.1016/j.aanat.2015.03.006
Choleris E, Thomas AW, Kavaliers M, Prato FS. A detailed ethological analysis of the mouse open field test: effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field. Neurosci Biobehav Rev. 2001;25:235–60.
pubmed: 11378179
doi: 10.1016/S0149-7634(01)00011-2
Angoa-Pérez M, Kane MJ, Briggs DI, Francescutti DM, Kuhn DM. Marble burying and nestlet shredding as tests of repetitive, compulsive-like behaviors in mice. J Vis Exp 2013;82:50978.
Ferhat AT, Halbedl S, Schmeisser MJ, Kas MJ, Bourgeron T, Ey E. Behavioural Phenotypes and Neural Circuit Dysfunctions in Mouse Models of Autism Spectrum Disorder. Adv Anat Embryol Cell Biol. 2017;224:85–101.
pubmed: 28551752
doi: 10.1007/978-3-319-52498-6_5
Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57:67–81.
pubmed: 15546155
doi: 10.1002/ana.20315
Zimmerman AW, Jyonouchi H, Comi AM, Connors SL, Milstien S, Varsou A, et al. Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr Neurol. 2005;33:195–201.
pubmed: 16139734
doi: 10.1016/j.pediatrneurol.2005.03.014
Chez MG, Dowling T, Patel PB, Khanna P, Kominsky M. Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol. 2007;36:361–5.
pubmed: 17560496
doi: 10.1016/j.pediatrneurol.2007.01.012
Croonenberghs J, Bosmans E, Deboutte D, Kenis G, Maes M. Activation of the inflammatory response system in autism. Neuropsychobiology. 2002;45:1–6.
pubmed: 11803234
doi: 10.1159/000048665
Molloy CA, Morrow AL, Meinzen-Derr J, Schleifer K, Dienger K, Manning-Courtney P, et al. Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol. 2006;172:198–205.
pubmed: 16360218
doi: 10.1016/j.jneuroim.2005.11.007
Malkova NV, Yu CZ, Hsiao EY, Moore MJ, Patterson PH. Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain Behav Immun. 2012;26:607–16.
pubmed: 22310922
pmcid: 3322300
doi: 10.1016/j.bbi.2012.01.011
Knuesel I, Chicha L, Britschgi M, Schobel SA, Bodmer M, Hellings JA, et al. Maternal immune activation and abnormal brain development across CNS disorders. Nat Rev Neurol. 2014;10:643–60.
pubmed: 25311587
doi: 10.1038/nrneurol.2014.187
Shi L, Fatemi SH, Sidwell RW, Patterson PH. Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci. 2003;23:297–302.
pubmed: 12514227
pmcid: 6742135
doi: 10.1523/JNEUROSCI.23-01-00297.2003
Boksa P. Effects of prenatal infection on brain development and behavior: a review of findings from animal models. Brain Behav Immun. 2010;24:881–97.
pubmed: 20230889
doi: 10.1016/j.bbi.2010.03.005
Patterson PH. Maternal infection and autism. Brain Behav Immun. 2012;26:393.
pubmed: 22001185
doi: 10.1016/j.bbi.2011.09.008
Smith SE, Li J, Garbett K, Mirnics K, Patterson PH. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci. 2007;27:10695–702.
pubmed: 17913903
pmcid: 2387067
doi: 10.1523/JNEUROSCI.2178-07.2007
Wilder PT, Varney KM, Weiss MB, Gitti RK, Weber DJ. Solution structure of zinc- and calcium-bound rat S100B as determined by nuclear magnetic resonance spectroscopy. Biochemistry. 2005;44:5690–702.
pubmed: 15823027
doi: 10.1021/bi0475830
Charpentier TH, Wilder PT, Liriano MA, Varney KM, Pozharski E, MacKerell AD Jr, et al. Divalent metal ion complexes of S100B in the absence and presence of pentamidine. J Mol Biol. 2008;382:56–73.
pubmed: 18602402
pmcid: 2636698
doi: 10.1016/j.jmb.2008.06.047
Galvão MC, Chaves-Kirsten GP, Queiroz-Hazarbassanov N, Carvalho VM, Bernardi MM, Kirsten TB. Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation. Life Sci. 2015;120:54–60.
pubmed: 25445220
doi: 10.1016/j.lfs.2014.10.019
Kirsten TB, Chaves-Kirsten GP, Bernardes S, Scavone C, Sarkis JE, Bernardi MM, et al. Lipopolysaccharide Exposure Induces Maternal Hypozincemia, and Prenatal Zinc Treatment Prevents Autistic-Like Behaviors and Disturbances in the Striatal Dopaminergic and mTOR Systems of Offspring. PLoS ONE. 2015;10:e0134565.
pubmed: 26218250
pmcid: 4517817
doi: 10.1371/journal.pone.0134565
Kirsten TB, Queiroz-Hazarbassanov N, Bernardi MM, Felicio LF. Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure. Life Sci. 2015;130:12–7.
pubmed: 25817235
doi: 10.1016/j.lfs.2015.02.027
Mousaviyan R, Davoodian N, Alizadeh F, Ghasemi-Kasman M, Mousavi SA, Shaerzadeh F, et al. Zinc Supplementation During Pregnancy Alleviates Lipopolysaccharide-Induced Glial Activation and Inflammatory Markers Expression in a Rat Model of Maternal Immune Activation. Biol Trace Elem Res. 2021;199:4193–204.
pubmed: 33400154
doi: 10.1007/s12011-020-02553-6
Pfaender S, Grabrucker AM. Characterization of biometal profiles in neurological disorders. Metallomics. 2014;6:960–77.
pubmed: 24643462
doi: 10.1039/C4MT00008K
Wang X, Xu Q, Bey AL, Lee Y, Jiang YH. Transcriptional and functional complexity of Shank3 provides a molecular framework to understand the phenotypic heterogeneity of SHANK3 causing autism and Shank3 mutant mice. Mol Autism. 2014;5:30.
pubmed: 25071925
pmcid: 4113141
doi: 10.1186/2040-2392-5-30
Leclerc E, Sturchler E, Vetter SW. The S100B/RAGE Axis in Alzheimer’s Disease. Cardiovasc Psychiatry Neurol. 2010;2010:539581.
pubmed: 20672051
pmcid: 2905692
doi: 10.1155/2010/539581
Usui A, Kato K, Abe T, Murase M, Tanaka M, Takeuchi E. S-100ao protein in blood and urine during open-heart surgery. Clin Chem. 1989;35:1942–44.
pubmed: 2776321
doi: 10.1093/clinchem/35.9.1942
Zaigham M, Lundberg F, Olofsson P. Protein S100B in umbilical cord blood as a potential biomarker of hypoxic-ischemic encephalopathy in asphyxiated newborns. Early Hum Dev. 2017;112:48–53.
pubmed: 28756088
doi: 10.1016/j.earlhumdev.2017.07.015
Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, et al. S100B’s double life: intracellular regulator and extracellular signal. Biochim Biophys Acta. 2009;1793:1008–22.
pubmed: 19110011
doi: 10.1016/j.bbamcr.2008.11.009
Gerlai R, Wojtowicz JM, Marks A, Roder J. Overexpression of a calcium-binding protein, S100 beta, in astrocytes alters synaptic plasticity and impairs spatial learning in transgenic mice. Learn Mem. 1995;2:26–39.
pubmed: 10467564
doi: 10.1101/lm.2.1.26
Raynaud F, Janossy A, Dahl J, Bertaso F, Perroy J, Varrault A, et al. Shank3-Rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation. J Neurosci. 2013;33:9699–715.
pubmed: 23739967
pmcid: 6619703
doi: 10.1523/JNEUROSCI.2725-12.2013
Nishiyama H, Knopfel T, Endo S, Itohara S. Glial protein S100B modulates long-term neuronal synaptic plasticity. Proc Natl Acad Sci USA. 2002;99:4037–42.
pubmed: 11891290
pmcid: 122644
doi: 10.1073/pnas.052020999
Won H, Lee HR, Gee HY, Mah W, Kim JI, Lee J, et al. Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function. Nature. 2012;486:261–5.
pubmed: 22699620
doi: 10.1038/nature11208
Bozdagi O, Sakurai T, Papapetrou D, Wang X, Dickstein DL, Takahashi N, et al. Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol Autism. 2010;1:15.
pubmed: 21167025
pmcid: 3019144
doi: 10.1186/2040-2392-1-15
Yang M, Bozdagi O, Scattoni ML, Wöhr M, Roullet FI, Katz AM, et al. Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J Neurosci. 2012;32:6525–41.
pubmed: 22573675
pmcid: 3362928
doi: 10.1523/JNEUROSCI.6107-11.2012
Wang X, McCoy PA, Rodriguiz RM, Pan Y, Je HS, Roberts AC, et al. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet. 2011;20:3093–108.
pubmed: 21558424
pmcid: 3131048
doi: 10.1093/hmg/ddr212
Peça J, Feliciano C, Ting JT, Wang W, Wells MF, Venkatraman TN, et al. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature. 2011;472:437–42.
pubmed: 21423165
pmcid: 3090611
doi: 10.1038/nature09965
Hung AY, Futai K, Sala C, Valtschanoff JG, Ryu J, Woodworth MA, et al. Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. J Neurosci. 2008;28:1697–1708.
pubmed: 18272690
pmcid: 2633411
doi: 10.1523/JNEUROSCI.3032-07.2008
Silverman JL, Turner SM, Barkan CL, Tolu SS, Saxena R, Hung AY, et al. Sociability and motor functions in Shank1 mutant mice. Brain Res. 2011;1380:120–37.
pubmed: 20868654
doi: 10.1016/j.brainres.2010.09.026
Wöhr M, Roullet FI, Hung AY, Sheng M, Crawley JN. Communication impairments in mice lacking Shank1: reduced levels of ultrasonic vocalizations and scent marking behavior. PLoS ONE. 2011;6:e20631.
pubmed: 21695253
pmcid: 3111434
doi: 10.1371/journal.pone.0020631
Crawley JN. Mouse behavioral assays relevant to the symptoms of autism. Brain Pathol. 2007;17:448–59.
pubmed: 17919130
pmcid: 8095652
doi: 10.1111/j.1750-3639.2007.00096.x
Moy SS, Nadler JJ, Young NB, Perez A, Holloway LP, Barbaro RP, et al. Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains. Behav Brain Res. 2007;176:4–20.
pubmed: 16971002
doi: 10.1016/j.bbr.2006.07.030
Sauer AK, Bockmann J, Steinestel K, Boeckers TM, Grabrucker AM. Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model. Int J Mol Sci. 20, (2019). https://doi.org/10.3390/ijms20092134
Sgritta M, Dooling SW, Buffington SA, Momin EN, Francis MB, Britton RA, et al. Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder. Neuron. 2019;101:246–259.e6.
pubmed: 30522820
doi: 10.1016/j.neuron.2018.11.018
Tabouy L, Getselter D, Ziv O, Karpuj M, Tabouy T, Lukic I, et al. Dysbiosis of microbiome and probiotic treatment in a genetic model of autism spectrum disorders. Brain Behav Immun. 2018;73:310–19.
pubmed: 29787855
doi: 10.1016/j.bbi.2018.05.015
Botelho HM, Fritz G, Gomes CM. Analysis of S100 oligomers and amyloids. Methods Mol Biol. 2012;849:373–86.
pubmed: 22528103
doi: 10.1007/978-1-61779-551-0_25
Yamaguchi H, Hara Y, Ago Y, Takano E, Hasebe S, Nakazawa T, et al. Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice. Behav Brain Res. 2017;333:67–73.
pubmed: 28655565
doi: 10.1016/j.bbr.2017.06.035
Ponzoni L, Moretti M, Sala M, Fasoli F, Mucchietto V, Lucini V, et al. Different physiological and behavioural effects of e-cigarette vapour and cigarette smoke in mice. Eur Neuropsychopharmacol. 2015;25:1775–86.
pubmed: 26141510
doi: 10.1016/j.euroneuro.2015.06.010
Bourin M, Hascoët M. The mouse light/dark box test. Eur J Pharm. 2003;463:55–65.
doi: 10.1016/S0014-2999(03)01274-3
Chen Y, Mao Y, Zhou D, Hu X, Wang J, Ma Y. Environmental enrichment and chronic restraint stress in ICR mice: effects on prepulse inhibition of startle and Y-maze spatial recognition memory. Behav Brain Res. 2010;212:49–55.
pubmed: 20359501
doi: 10.1016/j.bbr.2010.03.033
Zanardi A, Ferrari R, Leo G, Maskos U, Changeux JP, Zoli M. Loss of high-affinity nicotinic receptors increases the vulnerability to excitotoxic lesion and decreases the positive effects of an enriched environment. FASEB J. 2007;21:4028–37.
pubmed: 17622669
doi: 10.1096/fj.07-8260com
Stover KR, O´Leary TP, Brown RE. A Computer-Based Application for Rapid Unbiased Classification of Swim Paths in the Morris Water Maze. In: Spink AJ, Grieco F, Krips OE, Loijens LWS, Noldus LPJJ, Zimmerman PH, editors. Proceedings of Measuring Behavior. Eighth International Conference on Methods and Techniques in Behavioral Research; Noldus Information Technology, Utrecht, The Netherlands; 2012. p. 353–357.
Koolhaas JM, Coppens CM, de Boer SF, Buwalda B, Meerlo P, Timmermans PJ. The resident-intruder paradigm: a standardized test for aggression, violence and social stress. J Vis Exp. 2013;77:e4367.
Jirkof P. Burrowing and nest building behavior as indicators of well-being in mice. J Neurosci Methods. 2014;234:139–46.
pubmed: 24525328
doi: 10.1016/j.jneumeth.2014.02.001