Home > Publications Database > Disrupted extracellular matrix and cell cycle genes in autism-associated Shank3 deficiency are targeted by lithium. > print

001     270139
005     20240808164651.0
024 7 _ |a pmc:PMC11153165
|2 pmc
024 7 _ |a 10.1038/s41380-023-02362-y
|2 doi
024 7 _ |a pmid:38123724
|2 pmid
024 7 _ |a 1359-4184
|2 ISSN
024 7 _ |a 1476-5578
|2 ISSN
024 7 _ |a altmetric:157669533
|2 altmetric
037 _ _ |a DZNE-2024-00739
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Ioannidis, Valentin
|0 0000-0001-5182-7102
|b 0
245 _ _ |a Disrupted extracellular matrix and cell cycle genes in autism-associated Shank3 deficiency are targeted by lithium.
260 _ _ |a London
|c 2024
|b Macmillan
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1717675476_31718
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a The Shank3 gene encodes the major postsynaptic scaffolding protein SHANK3. Its mutation causes a syndromic form of autism spectrum disorder (ASD): Phelan-McDermid Syndrome (PMDS). It is characterized by global developmental delay, intellectual disorders (ID), ASD behavior, affective symptoms, as well as extra-cerebral symptoms. Although Shank3 deficiency causes a variety of molecular alterations, they do not suffice to explain all clinical aspects of this heterogenic syndrome. Since global gene expression alterations in Shank3 deficiency remain inadequately studied, we explored the transcriptome in vitro in primary hippocampal cells from Shank3∆11(-/-) mice, under control and lithium (Li) treatment conditions, and confirmed the findings in vivo. The Shank3∆11(-/-) genotype affected the overall transcriptome. Remarkably, extracellular matrix (ECM) and cell cycle transcriptional programs were disrupted. Accordingly, in the hippocampi of adolescent Shank3∆11(-/-) mice we found proteins of the collagen family and core cell cycle proteins downregulated. In vitro Li treatment of Shank3∆11(-/-) cells had a rescue-like effect on the ECM and cell cycle gene sets. Reversed ECM gene sets were part of a network, regulated by common transcription factors (TF) such as cAMP responsive element binding protein 1 (CREB1) and β-Catenin (CTNNB1), which are known downstream effectors of synaptic activity and targets of Li. These TFs were less abundant and/or hypo-phosphorylated in hippocampi of Shank3∆11(-/-) mice and could be rescued with Li in vitro and in vivo. Our investigations suggest the ECM compartment and cell cycle genes as new players in the pathophysiology of Shank3 deficiency, and imply involvement of transcriptional regulators, which can be modulated by Li. This work supports Li as potential drug in the management of PMDS symptoms, where a Phase III study is ongoing.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
|0 G:(DE-HGF)POF4-352
|c POF4-352
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Shank3 protein, mouse
|2 NLM Chemicals
650 _ 7 |a Nerve Tissue Proteins
|2 NLM Chemicals
650 _ 7 |a beta Catenin
|2 NLM Chemicals
650 _ 7 |a Creb1 protein, mouse
|2 NLM Chemicals
650 _ 7 |a Cyclic AMP Response Element-Binding Protein
|2 NLM Chemicals
650 _ 7 |a CTNNB1 protein, mouse
|2 NLM Chemicals
650 _ 7 |a Lithium
|0 9FN79X2M3F
|2 NLM Chemicals
650 _ 7 |a Microfilament Proteins
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Nerve Tissue Proteins: genetics
|2 MeSH
650 _ 2 |a Nerve Tissue Proteins: metabolism
|2 MeSH
650 _ 2 |a Hippocampus: metabolism
|2 MeSH
650 _ 2 |a Extracellular Matrix: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a beta Catenin: metabolism
|2 MeSH
650 _ 2 |a beta Catenin: genetics
|2 MeSH
650 _ 2 |a Chromosome Disorders: genetics
|2 MeSH
650 _ 2 |a Chromosome Disorders: metabolism
|2 MeSH
650 _ 2 |a Chromosome Deletion
|2 MeSH
650 _ 2 |a Cell Cycle: drug effects
|2 MeSH
650 _ 2 |a Cell Cycle: genetics
|2 MeSH
650 _ 2 |a Autistic Disorder: genetics
|2 MeSH
650 _ 2 |a Autistic Disorder: metabolism
|2 MeSH
650 _ 2 |a Chromosomes, Human, Pair 22: genetics
|2 MeSH
650 _ 2 |a Cyclic AMP Response Element-Binding Protein: metabolism
|2 MeSH
650 _ 2 |a Cyclic AMP Response Element-Binding Protein: genetics
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Transcriptome: genetics
|2 MeSH
650 _ 2 |a Autism Spectrum Disorder: genetics
|2 MeSH
650 _ 2 |a Autism Spectrum Disorder: metabolism
|2 MeSH
650 _ 2 |a Autism Spectrum Disorder: drug therapy
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Lithium: pharmacology
|2 MeSH
650 _ 2 |a Microfilament Proteins: metabolism
|2 MeSH
650 _ 2 |a Microfilament Proteins: genetics
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
700 1 _ |a Pandey, Rakshita
|b 1
700 1 _ |a Bauer, Helen Friedericke
|b 2
700 1 _ |a Schön, Michael
|b 3
700 1 _ |a Bockmann, Jürgen
|b 4
700 1 _ |a Boeckers, Tobias M
|0 P:(DE-2719)2812855
|b 5
700 1 _ |a Lutz, Anne-Kathrin
|0 0000-0002-3972-2057
|b 6
773 _ _ |a 10.1038/s41380-023-02362-y
|g Vol. 29, no. 3, p. 704 - 717
|0 PERI:(DE-600)1502531-7
|n 3
|p 704 - 717
|t Molecular psychiatry
|v 29
|y 2024
|x 1359-4184
856 4 _ |y OpenAccess
|u https://pub.dzne.de/record/270139/files/DZNE-2024-00739.pdf
856 4 _ |y OpenAccess
|x pdfa
|u https://pub.dzne.de/record/270139/files/DZNE-2024-00739.pdf?subformat=pdfa
909 C O |o oai:pub.dzne.de:270139
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 5
|6 P:(DE-2719)2812855
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-352
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms
|x 0
914 1 _ |y 2024
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2023-08-25
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2023-08-25
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2023-08-25
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2023-08-25
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
|d 2023-08-25
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b MOL PSYCHIATR : 2022
|d 2023-08-25
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2023-08-25
915 _ _ |a IF >= 10
|0 StatID:(DE-HGF)9910
|2 StatID
|b MOL PSYCHIATR : 2022
|d 2023-08-25
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2023-08-25
915 _ _ |a DEAL Springer
|0 StatID:(DE-HGF)3002
|2 StatID
|d 2023-08-25
|w ger
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2023-08-25
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
|d 2023-08-25
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2023-08-25
915 _ _ |a Creative Commons Attribution CC BY 4.0
|0 LIC:(DE-HGF)CCBY4
|2 HGFVOC
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2023-08-25
920 1 _ |0 I:(DE-2719)1910002
|k AG Böckers
|l Translational Protein Biochemistry
|x 0
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-2719)1910002
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21