Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction
Purposeful induction of fever for healing, including the treatment of epilepsy, was used over 2000 years ago by Hippocrates. More recently, fever has been demonstrated to rescue behavioral abnormalities in children with autism. However, the mechanism of fever benefit has remained elusive due in larg...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3924 |
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| author | Reem Jada Veronika Borisov Eliezer Laury Shmuel Halpert Nina S. Levy Shlomo Wagner Shai Netser Randall Walikonis Ido Carmi Shai Berlin Andrew P. Levy |
| author_facet | Reem Jada Veronika Borisov Eliezer Laury Shmuel Halpert Nina S. Levy Shlomo Wagner Shai Netser Randall Walikonis Ido Carmi Shai Berlin Andrew P. Levy |
| author_sort | Reem Jada |
| collection | DOAJ |
| description | Purposeful induction of fever for healing, including the treatment of epilepsy, was used over 2000 years ago by Hippocrates. More recently, fever has been demonstrated to rescue behavioral abnormalities in children with autism. However, the mechanism of fever benefit has remained elusive due in large part to the lack of appropriate human disease models recapitulating the fever effect. Pathological mutations in the IQSEC2 gene are frequently seen in children presenting with intellectual disability, autism and epilepsy. We recently described a murine A350V IQSEC2 disease model, which recapitulates important aspects of the human A350V IQSEC2 disease phenotype and the favorable response to a prolonged and sustained rise in body core temperature in a child with the mutation. Our goal has been to use this system to understand the mechanism of fever benefit and then develop drugs that can mimic this effect and reduce IQSEC2-associated morbidity. In this study, we first demonstrate a reduction in seizures in the mouse model following brief periods of heat therapy, similar to what was observed in a child with the mutation. We then show that brief heat therapy is associated with the correction of synaptic dysfunction in neuronal cultures of A350V mice, likely mediated by Arf6-GTP. |
| first_indexed | 2024-03-11T08:41:51Z |
| format | Article |
| id | doaj.art-60e7b023ef9a4638bceb4044175ea269 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:41:51Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-60e7b023ef9a4638bceb4044175ea2692023-11-16T21:06:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244392410.3390/ijms24043924Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic DysfunctionReem Jada0Veronika Borisov1Eliezer Laury2Shmuel Halpert3Nina S. Levy4Shlomo Wagner5Shai Netser6Randall Walikonis7Ido Carmi8Shai Berlin9Andrew P. Levy10Technion Faculty of Medicine, Technion Israel Institute of Technology, Haifa 3200003, IsraelTechnion Faculty of Medicine, Technion Israel Institute of Technology, Haifa 3200003, IsraelTechnion Faculty of Medicine, Technion Israel Institute of Technology, Haifa 3200003, IsraelTechnion Faculty of Medicine, Technion Israel Institute of Technology, Haifa 3200003, IsraelTechnion Faculty of Medicine, Technion Israel Institute of Technology, Haifa 3200003, IsraelSagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, IsraelSagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, IsraelDepartment of Physiology, University of Connecticutt, Storrs, CT 06269, USATechnion Faculty of Medicine, Technion Israel Institute of Technology, Haifa 3200003, IsraelTechnion Faculty of Medicine, Technion Israel Institute of Technology, Haifa 3200003, IsraelTechnion Faculty of Medicine, Technion Israel Institute of Technology, Haifa 3200003, IsraelPurposeful induction of fever for healing, including the treatment of epilepsy, was used over 2000 years ago by Hippocrates. More recently, fever has been demonstrated to rescue behavioral abnormalities in children with autism. However, the mechanism of fever benefit has remained elusive due in large part to the lack of appropriate human disease models recapitulating the fever effect. Pathological mutations in the IQSEC2 gene are frequently seen in children presenting with intellectual disability, autism and epilepsy. We recently described a murine A350V IQSEC2 disease model, which recapitulates important aspects of the human A350V IQSEC2 disease phenotype and the favorable response to a prolonged and sustained rise in body core temperature in a child with the mutation. Our goal has been to use this system to understand the mechanism of fever benefit and then develop drugs that can mimic this effect and reduce IQSEC2-associated morbidity. In this study, we first demonstrate a reduction in seizures in the mouse model following brief periods of heat therapy, similar to what was observed in a child with the mutation. We then show that brief heat therapy is associated with the correction of synaptic dysfunction in neuronal cultures of A350V mice, likely mediated by Arf6-GTP.https://www.mdpi.com/1422-0067/24/4/3924feverheat therapyIQSEC2AMPA receptorArf6-GTP |
| spellingShingle | Reem Jada Veronika Borisov Eliezer Laury Shmuel Halpert Nina S. Levy Shlomo Wagner Shai Netser Randall Walikonis Ido Carmi Shai Berlin Andrew P. Levy Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction International Journal of Molecular Sciences fever heat therapy IQSEC2 AMPA receptor Arf6-GTP |
| title | Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction |
| title_full | Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction |
| title_fullStr | Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction |
| title_full_unstemmed | Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction |
| title_short | Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction |
| title_sort | daily brief heat therapy reduces seizures in a350v iqsec2 mice and is associated with correction of ampa receptor mediated synaptic dysfunction |
| topic | fever heat therapy IQSEC2 AMPA receptor Arf6-GTP |
| url | https://www.mdpi.com/1422-0067/24/4/3924 |
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