Behavioral phenotyping identifies autism-like repetitive stereotypies in a Tsc2 haploinsufficient rat model
Abstract Besides deficits in social communication and interaction, repetitive behavior patterns are core manifestations of autism spectrum disorder (ASD). Phenotypes are heterogeneous and can range from simple lower-order motor stereotypies to more complex higher-order cognitive inflexibility and fi...
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BMC
2025-07-01
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| Series: | Behavioral and Brain Functions |
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| Online Access: | https://doi.org/10.1186/s12993-025-00284-z |
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| author | Antonia Ramme Mirjam Zachow Bettina Habelt Iveta Vojtechova Tomas Petrasek Robert Waltereit Nadine Bernhardt |
| author_facet | Antonia Ramme Mirjam Zachow Bettina Habelt Iveta Vojtechova Tomas Petrasek Robert Waltereit Nadine Bernhardt |
| author_sort | Antonia Ramme |
| collection | DOAJ |
| description | Abstract Besides deficits in social communication and interaction, repetitive behavior patterns are core manifestations of autism spectrum disorder (ASD). Phenotypes are heterogeneous and can range from simple lower-order motor stereotypies to more complex higher-order cognitive inflexibility and fixated interests. Due to ASD’s multifaceted etiology, animal models are often generated from monogenic diseases associated with ASD, such as Tuberous Sclerosis Complex (TSC), and are expected to copy behavioral core deficits to increase the model´s translational value for ASD disease research and novel treatment development. The global haploinsufficient Tsc2 +/− Eker rat model has been shown to display ASD core symptoms in the social domain. However, the presence and extent of aberrant repetitive behavior patterns in the Eker rat remain to be investigated. Thus, the present study applied a set of behavioral tests to determine the repetitive behavioral profile in Tsc2 +/− Eker rats and used brain-region-specific neurotransmitter analysis to support findings on a molecular level. Tsc2 +/− animals demonstrated lower-order repetitive behavior in the form of excessive self-grooming and nestlet shredding under non-stressful conditions that co-occurred alongside social interaction deficits. However, no higher-order repetitive behavior was detected in Tsc2 +/− rats. Interestingly, Tsc2 +/− rats exhibited increased levels of homeostatic dopamine in the prefrontal cortex, supporting the link between aberrant cortical dopaminergic transmission and the appearance of lower-order repetitive phenotypes. Together, our results support the Tsc2 +/− Eker rat as a model of ASD-like behavior for further investigation of ASD-related development and neurobiology. |
| format | Article |
| id | doaj-art-28874d33e628463dab3f89fece6d4abc |
| institution | DOAJ |
| issn | 1744-9081 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Behavioral and Brain Functions |
| spelling | doaj-art-28874d33e628463dab3f89fece6d4abc2025-08-20T03:03:44ZengBMCBehavioral and Brain Functions1744-90812025-07-0121111610.1186/s12993-025-00284-zBehavioral phenotyping identifies autism-like repetitive stereotypies in a Tsc2 haploinsufficient rat modelAntonia Ramme0Mirjam Zachow1Bettina Habelt2Iveta Vojtechova3Tomas Petrasek4Robert Waltereit5Nadine Bernhardt6Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität DresdenDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität DresdenDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität DresdenNational Institute of Mental HealthNational Institute of Mental HealthDepartment of Child and Adolescent Psychiatry, University Medical CenterDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität DresdenAbstract Besides deficits in social communication and interaction, repetitive behavior patterns are core manifestations of autism spectrum disorder (ASD). Phenotypes are heterogeneous and can range from simple lower-order motor stereotypies to more complex higher-order cognitive inflexibility and fixated interests. Due to ASD’s multifaceted etiology, animal models are often generated from monogenic diseases associated with ASD, such as Tuberous Sclerosis Complex (TSC), and are expected to copy behavioral core deficits to increase the model´s translational value for ASD disease research and novel treatment development. The global haploinsufficient Tsc2 +/− Eker rat model has been shown to display ASD core symptoms in the social domain. However, the presence and extent of aberrant repetitive behavior patterns in the Eker rat remain to be investigated. Thus, the present study applied a set of behavioral tests to determine the repetitive behavioral profile in Tsc2 +/− Eker rats and used brain-region-specific neurotransmitter analysis to support findings on a molecular level. Tsc2 +/− animals demonstrated lower-order repetitive behavior in the form of excessive self-grooming and nestlet shredding under non-stressful conditions that co-occurred alongside social interaction deficits. However, no higher-order repetitive behavior was detected in Tsc2 +/− rats. Interestingly, Tsc2 +/− rats exhibited increased levels of homeostatic dopamine in the prefrontal cortex, supporting the link between aberrant cortical dopaminergic transmission and the appearance of lower-order repetitive phenotypes. Together, our results support the Tsc2 +/− Eker rat as a model of ASD-like behavior for further investigation of ASD-related development and neurobiology.https://doi.org/10.1186/s12993-025-00284-zAutism spectrum disorderTuberous sclerosis complexRepetitive behaviorEker rat |
| spellingShingle | Antonia Ramme Mirjam Zachow Bettina Habelt Iveta Vojtechova Tomas Petrasek Robert Waltereit Nadine Bernhardt Behavioral phenotyping identifies autism-like repetitive stereotypies in a Tsc2 haploinsufficient rat model Behavioral and Brain Functions Autism spectrum disorder Tuberous sclerosis complex Repetitive behavior Eker rat |
| title | Behavioral phenotyping identifies autism-like repetitive stereotypies in a Tsc2 haploinsufficient rat model |
| title_full | Behavioral phenotyping identifies autism-like repetitive stereotypies in a Tsc2 haploinsufficient rat model |
| title_fullStr | Behavioral phenotyping identifies autism-like repetitive stereotypies in a Tsc2 haploinsufficient rat model |
| title_full_unstemmed | Behavioral phenotyping identifies autism-like repetitive stereotypies in a Tsc2 haploinsufficient rat model |
| title_short | Behavioral phenotyping identifies autism-like repetitive stereotypies in a Tsc2 haploinsufficient rat model |
| title_sort | behavioral phenotyping identifies autism like repetitive stereotypies in a tsc2 haploinsufficient rat model |
| topic | Autism spectrum disorder Tuberous sclerosis complex Repetitive behavior Eker rat |
| url | https://doi.org/10.1186/s12993-025-00284-z |
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