The Role of Synaptic Cell Adhesion Molecules and Associated Scaffolding Proteins in Social Affiliative Behaviors

Taylor, Sara; Ferri, Sarah L.; Grewal, Mahip; Smernoff, Zoe; Bućan, Maja; Weiner, Joshua A.; Brodkin, Edward S.

doi:10.1016/j.biopsych.2020.02.012

Cited by 36 publications

(32 citation statements)

References 132 publications

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“…Additionally, we observed that two probes, cg08447324 (Δβ = 0.117, P = 7.212e-05) and cg16658931 (Δβ = 0.114, P = 7.286e-05) in SHANK1 , and two probes (cg10911054 (Δβ = 0.132, P = 2.207e-06) and cg18080819 (Δβ = 0.126, P = 1.984e-04) in SHANK2 also showed hypermethylation in the high-dose haloperidol group. SHANK genes encode scaffold proteins in postsynaptic neurons and are involved in neuropsychiatric disorders ( Kursula, 2019 ; Taylor et al, 2020 ). Epigenetic regulation of SHANK genes by antipsychotics affects a broad range of neuronal functions.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive DNA Methylation Analysis of Human Neuroblastoma Cells Treated With Haloperidol and Risperidone

Nakachi

Kiyono

et al. 2021

Front. Mol. Neurosci.

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Accumulating evidence suggests that the epigenetic alterations induced by antipsychotics contribute to the therapeutic efficacy. However, global and site-specific epigenetic changes by antipsychotics and those shared by different classes of antipsychotics remain poorly understood. We conducted a comprehensive DNA methylation analysis of human neuroblastoma cells cultured with antipsychotics. The cells were cultured with low and high concentrations of haloperidol or risperidone for 8 days. DNA methylation assay was performed with the Illumina HumanMethylation450 BeadChip. We found that both haloperidol and risperidone tended to cause hypermethylation changes and showed similar DNA methylation changes closely related to neuronal functions. A total of 294 differentially methylated probes (DMPs), including 197 hypermethylated and 97 hypomethylated DMPs, were identified with both haloperidol and risperidone treatment. Gene ontology analysis of the hypermethylated probe-associated genes showed enrichment of genes related to the regulation of neurotransmitter receptor activity and lipoprotein lipase activity. Pathway analysis identified that among the DMP-associated genes, SHANK1 and SHANK2 were the major genes in the neuropsychiatric disorder-related pathways. Our data would be valuable for understanding the mechanisms of action of antipsychotics from an epigenetic viewpoint.

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Section: Discussionmentioning

confidence: 99%

Comprehensive DNA Methylation Analysis of Human Neuroblastoma Cells Treated With Haloperidol and Risperidone

Nakachi

Kiyono

et al. 2021

Front. Mol. Neurosci.

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“…Synaptopodin ( synpo ; 36), the parkinson’s disease-associated synaptic vesicle endocytosis protein dnajc6/auxilin (37), Neurotrophin 5 ( ntf5; 38), glutamate ionotropic receptor kainate type subunit 5 ( grik5; 39 ), the autism spectrum disorder-associated candidate shank2 (40), and the transcription factor neurod1 which plays a crucial role in neuronal cell fate specification (41). Plasticity adaptations are crucially involved in adaptive learning and memory processes including emotional and social memories (42). Moreover, these adaptations enable neuronal networks to stabilise activity in the face of external perturbations.…”

Section: Discussionmentioning

confidence: 99%

Reconceptualising resilience within a translational framework is supported by unique and brain-region specific transcriptional signatures in mice

Ayash

Lingner

Ryu

et al. 2020

Preprint

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Chronic social defeat (CSD) in mice has been increasingly employed in experimental resilience research. Particularly, the degree of CSD-induced social avoidance is used to classify animals into resilient (socially non-avoidant) versus susceptible (avoidant). In-spired by human data pointing to threat-safety discrimination and responsiveness to extinction training of aversive memories as characteristics of resilient individuals, we here describe a translationally informed stratification which identified three phenotypic subgroups of mice following CSD: the Discriminating-avoiders, characterised by successful social threat-safety discrimination and successful extinction of social avoidance; the Indis-criminate-avoiders, showing aversive response generalisation, and the Non-avoiders (absence of social avoidance) displaying impaired conditioned learning. Furthermore, and supporting the biological validity of our approach, we uncovered subgroup-specific transcriptional signatures in classical fear conditioning and anxiety-related brain regions. Our reconceptualisation of resilience in mice refines the currently used dichotomous classification and contributes to advancing future translational approaches.

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“…As shown in Figure 2 A, DLGAP2 interacts with SHANK1–2, DLG2-4 and DLGAP1-2-3. Disruption of the network of scaffolding proteins alters the homeostasis of the PSD, contributing to various neuropsychiatric conditions, such as autism spectrum disorders, intellectual disability, behavioral problems, schizophrenia, and bipolar disorders [ 16 , 58 , 59 , 60 , 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

8p23.2-pter Microdeletions: Seven New Cases Narrowing the Candidate Region and Review of the Literature

Catusi

Garzo

Capra

et al. 2021

Genes

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To date only five patients with 8p23.2-pter microdeletions manifesting a mild-to-moderate cognitive impairment and/or developmental delay, dysmorphisms and neurobehavioral issues were reported. The smallest microdeletion described by Wu in 2010 suggested a critical region (CR) of 2.1 Mb including several genes, out of which FBXO25, DLGAP2, CLN8, ARHGEF10 and MYOM2 are the main candidates. Here we present seven additional patients with 8p23.2-pter microdeletions, ranging from 71.79 kb to 4.55 Mb. The review of five previously reported and nine Decipher patients confirmed the association of the CR with a variable clinical phenotype characterized by intellectual disability/developmental delay, including language and speech delay and/or motor impairment, behavioral anomalies, autism spectrum disorder, dysmorphisms, microcephaly, fingers/toes anomalies and epilepsy. Genotype analysis allowed to narrow down the 8p23.3 candidate region which includes only DLGAP2, CLN8 and ARHGEF10 genes, accounting for the main signs of the broad clinical phenotype associated to 8p23.2-pter microdeletions. This region is more restricted compared to the previously proposed CR. Overall, our data favor the hypothesis that DLGAP2 is the actual strongest candidate for neurodevelopmental/behavioral phenotypes. Additional patients will be necessary to validate the pathogenic role of DLGAP2 and better define how the two contiguous genes, ARHGEF10 and CLN8, might contribute to the clinical phenotype.

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The Role of Synaptic Cell Adhesion Molecules and Associated Scaffolding Proteins in Social Affiliative Behaviors

Cited by 36 publications

References 132 publications

Comprehensive DNA Methylation Analysis of Human Neuroblastoma Cells Treated With Haloperidol and Risperidone

Comprehensive DNA Methylation Analysis of Human Neuroblastoma Cells Treated With Haloperidol and Risperidone

Reconceptualising resilience within a translational framework is supported by unique and brain-region specific transcriptional signatures in mice

8p23.2-pter Microdeletions: Seven New Cases Narrowing the Candidate Region and Review of the Literature

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