Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function
Abstract Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and the most prevalent monogenic cause of autism. Although the knockout (KO) of the Fmr1 gene homolog in mice is primarily used for elucidating the neurobiological substrate of FXS, there is limited ass...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-02-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-024-02815-0 |
| _version_ | 1797273092230217728 |
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| author | George Ntoulas Charalampos Brakatselos Gerasimos Nakas Michail-Zois Asprogerakas Foteini Delis Leonidas J. Leontiadis George Trompoukis Costas Papatheodoropoulos Dimitrios Gkikas Dimitrios Valakos Giannis Vatsellas Panagiotis K. Politis Alexia Polissidis Katerina Antoniou |
| author_facet | George Ntoulas Charalampos Brakatselos Gerasimos Nakas Michail-Zois Asprogerakas Foteini Delis Leonidas J. Leontiadis George Trompoukis Costas Papatheodoropoulos Dimitrios Gkikas Dimitrios Valakos Giannis Vatsellas Panagiotis K. Politis Alexia Polissidis Katerina Antoniou |
| author_sort | George Ntoulas |
| collection | DOAJ |
| description | Abstract Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and the most prevalent monogenic cause of autism. Although the knockout (KO) of the Fmr1 gene homolog in mice is primarily used for elucidating the neurobiological substrate of FXS, there is limited association of the experimental data with the pathophysiological condition in humans. The use of Fmr1 KO rats offers additional translational validity in this regard. Therefore, we employed a multi-level approach to study the behavioral profile and the glutamatergic and GABAergic neurotransmission status in pathophysiology-associated brain structures of Fmr1 KO rats, including the recordings of evoked and spontaneous field potentials from hippocampal slices, paralleled with next-generation RNA sequencing (RNA-seq). We found that these rats exhibit hyperactivity and cognitive deficits, along with characteristic bidirectional glutamatergic and GABAergic alterations in the prefrontal cortex and the hippocampus. These results are coupled to affected excitability and local inhibitory processes in the hippocampus, along with a specific transcriptional profile, highlighting dysregulated hippocampal network activity in KO rats. Overall, our data provide novel insights concerning the biobehavioral profile of FmR1 KO rats and translationally upscales our understanding on pathophysiology and symptomatology of FXS syndrome. |
| first_indexed | 2024-03-07T14:39:32Z |
| format | Article |
| id | doaj.art-35d64c5f4487448394be49984b01007d |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-07T14:39:32Z |
| publishDate | 2024-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-35d64c5f4487448394be49984b01007d2024-03-05T20:26:52ZengNature Publishing GroupTranslational Psychiatry2158-31882024-02-0114111210.1038/s41398-024-02815-0Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic functionGeorge Ntoulas0Charalampos Brakatselos1Gerasimos Nakas2Michail-Zois Asprogerakas3Foteini Delis4Leonidas J. Leontiadis5George Trompoukis6Costas Papatheodoropoulos7Dimitrios Gkikas8Dimitrios Valakos9Giannis Vatsellas10Panagiotis K. Politis11Alexia Polissidis12Katerina Antoniou13Department of Pharmacology, Faculty of Medicine, School of Health Sciences University of IoanninaDepartment of Pharmacology, Faculty of Medicine, School of Health Sciences University of IoanninaDepartment of Pharmacology, Faculty of Medicine, School of Health Sciences University of IoanninaDepartment of Pharmacology, Faculty of Medicine, School of Health Sciences University of IoanninaDepartment of Pharmacology, Faculty of Medicine, School of Health Sciences University of IoanninaLaboratory of Neurophysiology, Department of Medicine, University of PatrasLaboratory of Neurophysiology, Department of Medicine, University of PatrasLaboratory of Neurophysiology, Department of Medicine, University of PatrasCenter of Basic Research, Biomedical Research Foundation of the Academy of AthensCenter of Basic Research, Biomedical Research Foundation of the Academy of AthensCenter of Basic Research, Biomedical Research Foundation of the Academy of AthensCenter of Basic Research, Biomedical Research Foundation of the Academy of AthensDepartment of Pharmacology, Faculty of Medicine, School of Health Sciences University of IoanninaDepartment of Pharmacology, Faculty of Medicine, School of Health Sciences University of IoanninaAbstract Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and the most prevalent monogenic cause of autism. Although the knockout (KO) of the Fmr1 gene homolog in mice is primarily used for elucidating the neurobiological substrate of FXS, there is limited association of the experimental data with the pathophysiological condition in humans. The use of Fmr1 KO rats offers additional translational validity in this regard. Therefore, we employed a multi-level approach to study the behavioral profile and the glutamatergic and GABAergic neurotransmission status in pathophysiology-associated brain structures of Fmr1 KO rats, including the recordings of evoked and spontaneous field potentials from hippocampal slices, paralleled with next-generation RNA sequencing (RNA-seq). We found that these rats exhibit hyperactivity and cognitive deficits, along with characteristic bidirectional glutamatergic and GABAergic alterations in the prefrontal cortex and the hippocampus. These results are coupled to affected excitability and local inhibitory processes in the hippocampus, along with a specific transcriptional profile, highlighting dysregulated hippocampal network activity in KO rats. Overall, our data provide novel insights concerning the biobehavioral profile of FmR1 KO rats and translationally upscales our understanding on pathophysiology and symptomatology of FXS syndrome.https://doi.org/10.1038/s41398-024-02815-0 |
| spellingShingle | George Ntoulas Charalampos Brakatselos Gerasimos Nakas Michail-Zois Asprogerakas Foteini Delis Leonidas J. Leontiadis George Trompoukis Costas Papatheodoropoulos Dimitrios Gkikas Dimitrios Valakos Giannis Vatsellas Panagiotis K. Politis Alexia Polissidis Katerina Antoniou Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function Translational Psychiatry |
| title | Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function |
| title_full | Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function |
| title_fullStr | Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function |
| title_full_unstemmed | Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function |
| title_short | Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function |
| title_sort | multi level profiling of the fmr1 ko rat unveils altered behavioral traits along with aberrant glutamatergic function |
| url | https://doi.org/10.1038/s41398-024-02815-0 |
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