Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model
Abstract Background Until now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03787-9 |
| _version_ | 1811204004895522816 |
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| author | Lifei Xiao Shucai Jiang Yangyang Wang Caibin Gao Cuicui Liu Xianhao Huo Wenchao Li Baorui Guo Chaofan Wang Yu Sun Anni Wang Yan Feng Feng Wang Tao Sun |
| author_facet | Lifei Xiao Shucai Jiang Yangyang Wang Caibin Gao Cuicui Liu Xianhao Huo Wenchao Li Baorui Guo Chaofan Wang Yu Sun Anni Wang Yan Feng Feng Wang Tao Sun |
| author_sort | Lifei Xiao |
| collection | DOAJ |
| description | Abstract Background Until now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific brain circuits, has recently been considered as a promising intervention for neuropsychiatric disorders. Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability. Herein, we investigated the effects of continuous high-frequency deep brain stimulation in the anterior insula of rats exposed to VPA and explored cognitive functions, behavior, and molecular proteins connected to autism spectrum disorder. Methods VPA-exposed offspring were bilaterally implanted with electrodes in the anterior insula (Day 0) with a recovery period of 1 week. (Day 0–7). High-frequency deep brain stimulation was applied from days 11 to 29. Three behavioral tests, including three-chamber social interaction test, were performed on days 7, 13, 18, 25 and 36, and several rats were used for analysis of immediate early genes and proteomic after deep brain stimulation intervention. Meanwhile, animals were subjected to a 20 day spatial learning and cognitive rigidity test using IntelliCage on day 11. Results Deep brain stimulation improved the sociability and social novelty preference at day 18 prior to those at day 13, and the improvement has reached the upper limit compared to day 25. As for repetitive/stereotypic-like behavior, self- grooming time were reduced at day 18 and reached the upper limit, and the numbers of burried marbles were reduced at day 13 prior to those at day 18 and day 25. The improvements of sociability and social novelty preference were persistent after the stimulation had ceased. Spatial learning ability and cognitive rigidity were unaffected. We identified 35 proteins in the anterior insula, some of which were intimately linked to autism, and their expression levels were reversed upon administration of deep brain stimulation. Conclusions Autism-like behavior was ameliorated and autism-related proteins were reversed in the insula by deep brain stimulation intervention, these findings reveal that the insula may be a potential target for DBS in the treatment of autism, which provide a theoretical basis for its clinical application., although future studies are still warranted. |
| first_indexed | 2024-04-12T03:04:28Z |
| format | Article |
| id | doaj.art-e46b61a8fa7e4c76be0aec062dcf9519 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-12T03:04:28Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-e46b61a8fa7e4c76be0aec062dcf95192022-12-22T03:50:33ZengBMCJournal of Translational Medicine1479-58762022-12-0120112510.1186/s12967-022-03787-9Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat modelLifei Xiao0Shucai Jiang1Yangyang Wang2Caibin Gao3Cuicui Liu4Xianhao Huo5Wenchao Li6Baorui Guo7Chaofan Wang8Yu Sun9Anni Wang10Yan Feng11Feng Wang12Tao Sun13Ningxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical UniversityDepartment of Neurosurgery, Weifang People’s HospitalNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical UniversityDepartment of Neurosurgery, General Hospital of Ningxia Medical UniversityDepartment of Otolaryngology and Head Surgery, The First People’s Hospital of YinchuanNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical UniversityDepartment of Neurosurgery, Shaanxi Provincial People’s HospitalNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of MedicineNingxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical UniversityAbstract Background Until now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific brain circuits, has recently been considered as a promising intervention for neuropsychiatric disorders. Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability. Herein, we investigated the effects of continuous high-frequency deep brain stimulation in the anterior insula of rats exposed to VPA and explored cognitive functions, behavior, and molecular proteins connected to autism spectrum disorder. Methods VPA-exposed offspring were bilaterally implanted with electrodes in the anterior insula (Day 0) with a recovery period of 1 week. (Day 0–7). High-frequency deep brain stimulation was applied from days 11 to 29. Three behavioral tests, including three-chamber social interaction test, were performed on days 7, 13, 18, 25 and 36, and several rats were used for analysis of immediate early genes and proteomic after deep brain stimulation intervention. Meanwhile, animals were subjected to a 20 day spatial learning and cognitive rigidity test using IntelliCage on day 11. Results Deep brain stimulation improved the sociability and social novelty preference at day 18 prior to those at day 13, and the improvement has reached the upper limit compared to day 25. As for repetitive/stereotypic-like behavior, self- grooming time were reduced at day 18 and reached the upper limit, and the numbers of burried marbles were reduced at day 13 prior to those at day 18 and day 25. The improvements of sociability and social novelty preference were persistent after the stimulation had ceased. Spatial learning ability and cognitive rigidity were unaffected. We identified 35 proteins in the anterior insula, some of which were intimately linked to autism, and their expression levels were reversed upon administration of deep brain stimulation. Conclusions Autism-like behavior was ameliorated and autism-related proteins were reversed in the insula by deep brain stimulation intervention, these findings reveal that the insula may be a potential target for DBS in the treatment of autism, which provide a theoretical basis for its clinical application., although future studies are still warranted.https://doi.org/10.1186/s12967-022-03787-9Autism spectrum disorderDeep brain stimulationInsula cortexValproic acidProteomics |
| spellingShingle | Lifei Xiao Shucai Jiang Yangyang Wang Caibin Gao Cuicui Liu Xianhao Huo Wenchao Li Baorui Guo Chaofan Wang Yu Sun Anni Wang Yan Feng Feng Wang Tao Sun Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model Journal of Translational Medicine Autism spectrum disorder Deep brain stimulation Insula cortex Valproic acid Proteomics |
| title | Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model |
| title_full | Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model |
| title_fullStr | Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model |
| title_full_unstemmed | Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model |
| title_short | Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model |
| title_sort | continuous high frequency deep brain stimulation of the anterior insula modulates autism like behavior in a valproic acid induced rat model |
| topic | Autism spectrum disorder Deep brain stimulation Insula cortex Valproic acid Proteomics |
| url | https://doi.org/10.1186/s12967-022-03787-9 |
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