Social Reward Learning Deficits and Concordant Brain Alterations in Rats Overexpressing Disrupted-in-Schizophrenia 1 (DISC1).
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| Názov: | Social Reward Learning Deficits and Concordant Brain Alterations in Rats Overexpressing Disrupted-in-Schizophrenia 1 (DISC1). |
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| Autori: | Dören J; Comparative Psychology, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Düsseldorf 40225, Germany doeren@hhu.de., Kupriyanova Y; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf 40225, Germany.; German Center for Diabetes Research (DZD), Partner Düsseldorf, Neuherberg 85764, Germany., Schäble S; Comparative Psychology, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Düsseldorf 40225, Germany., Troßbach S; Department of Neuropathology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf 40225, Germany., McGuire B; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London SE5 9RT, United Kingdom., Vernon AC; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London SE5 9RT, United Kingdom.; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, United Kingdom., Roden M; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf 40225, Germany.; German Center for Diabetes Research (DZD), Partner Düsseldorf, Neuherberg 85764, Germany.; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf 40225, Germany., Korth C; Department of Neuropathology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf 40225, Germany., Kalenscher T; Comparative Psychology, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Düsseldorf 40225, Germany. |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2025 Oct 29; Vol. 45 (44). Date of Electronic Publication: 2025 Oct 29. |
| Spôsob vydávania: | Journal Article |
| Jazyk: | English |
| Informácie o časopise: | Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Electronic Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE |
| Imprint Name(s): | Publication: Washington, DC : Society for Neuroscience Original Publication: [Baltimore, Md.] : The Society, c1981- |
| Výrazy zo slovníka MeSH: | Reward* , Nerve Tissue Proteins*/genetics , Nerve Tissue Proteins*/metabolism , Nerve Tissue Proteins*/biosynthesis , Brain*/pathology , Brain*/metabolism , Brain*/diagnostic imaging , Social Behavior* , Learning*/physiology , Learning Disabilities*/genetics , Learning Disabilities*/pathology, Animals ; Male ; Rats ; Rats, Transgenic ; Humans ; Diffusion Tensor Imaging ; Schizophrenia/genetics ; Disease Models, Animal |
| Abstrakt: | Social deficits are a hallmark of schizophrenia, often characterized by impairments in processing and integrating socially transmitted information. However, translational models that accurately capture these deficits remain scarce. The Disrupted-in-Schizophrenia 1 gene ( DISC1 ), a key susceptibility factor implicated in the etiology of psychiatric disorders, has been shown to cause DISC1 protein aggregation and dysfunctional signaling when modestly overexpressed, ultimately resulting in aberrant dopamine homeostasis. In this study, we employed a transgenic rat model overexpressing human DISC1 (tgDISC1 rats) to investigate social reward learning and microstructural integrity in the brain. Using a modified Social Transmission of Food Preference (STFP) task, we report that male tgDISC1 rats failed to update reward preferences based on social information, despite intact nonsocial reward learning-suggesting a specific deficit in social reward learning. Diffusion tensor imaging (DTI) in a behaviorally naive cohort revealed reduced fractional anisotropy (FA) in key subcortical regions, including the nucleus accumbens, amygdala, and substantia nigra, as well as areas mediating cortical-subcortical communication as the thalamus. Structural alterations in corresponding neuroanatomical areas have also been described in DTI of schizophrenia patients. Our findings link aberrant DISC1 signaling with impaired connectivity in parts of the mesolimbic system, critical for integrating social information into decision-making. This model recapitulates both behavioral and structural endophenotypes of schizophrenia and suggests that social impairments may stem from a fine-grained circuit-selective dysfunction rather than a generalized reward processing deficit. The tgDISC1 rat thus offers a translational platform for probing the neural substrates of social dysfunction in psychiatric disorders. (Copyright © 2025 the authors.) |
| Contributed Indexing: | Keywords: DISC1; diffusion tensor imaging; pathophysiology; rat model; schizophrenia; social reward learning |
| Substance Nomenclature: | 0 (Nerve Tissue Proteins) 0 (DISC1 protein, human) 0 (Disc1 protein, rat) |
| Entry Date(s): | Date Created: 20250911 Date Completed: 20251029 Latest Revision: 20251101 |
| Update Code: | 20251101 |
| PubMed Central ID: | PMC12572924 |
| DOI: | 10.1523/JNEUROSCI.1067-25.2025 |
| PMID: | 40935665 |
| Databáza: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Social deficits are a hallmark of schizophrenia, often characterized by impairments in processing and integrating socially transmitted information. However, translational models that accurately capture these deficits remain scarce. The Disrupted-in-Schizophrenia 1 gene ( DISC1 ), a key susceptibility factor implicated in the etiology of psychiatric disorders, has been shown to cause DISC1 protein aggregation and dysfunctional signaling when modestly overexpressed, ultimately resulting in aberrant dopamine homeostasis. In this study, we employed a transgenic rat model overexpressing human DISC1 (tgDISC1 rats) to investigate social reward learning and microstructural integrity in the brain. Using a modified Social Transmission of Food Preference (STFP) task, we report that male tgDISC1 rats failed to update reward preferences based on social information, despite intact nonsocial reward learning-suggesting a specific deficit in social reward learning. Diffusion tensor imaging (DTI) in a behaviorally naive cohort revealed reduced fractional anisotropy (FA) in key subcortical regions, including the nucleus accumbens, amygdala, and substantia nigra, as well as areas mediating cortical-subcortical communication as the thalamus. Structural alterations in corresponding neuroanatomical areas have also been described in DTI of schizophrenia patients. Our findings link aberrant DISC1 signaling with impaired connectivity in parts of the mesolimbic system, critical for integrating social information into decision-making. This model recapitulates both behavioral and structural endophenotypes of schizophrenia and suggests that social impairments may stem from a fine-grained circuit-selective dysfunction rather than a generalized reward processing deficit. The tgDISC1 rat thus offers a translational platform for probing the neural substrates of social dysfunction in psychiatric disorders.<br /> (Copyright © 2025 the authors.) |
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| ISSN: | 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.1067-25.2025 |