ArticleJournal of translational medicine2022
Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Systematic review and meta-analysis: multimodal functional and anatomical neural alterations in autism spectrum disorder.Molecular autism · 2024Pooled it
- Prenatal valproic acid exposure alters striatal proteomic signatures associated with autism spectrum disorder in mice.Translational psychiatry · 2026Article
- Hypoactivity, abnormal development of dendrites relevant to impaired synaptic transmission of calretinin-expressing interneurons in the medial prefrontal cortex underlies social deficits of mouse model in autism.Translational psychiatry · 2026Article
- Neuroplasticity mechanisms of NDBIs in autism: a review from brain connectivity to behavioral improvement.European journal of medical research · 2026Review
- Impaired Neuregulin 1 Processing is Associated with Synaptic and Behavioral Abnormalities in a Prenatal Valproic Acid Model of Autism.International journal of biological sciences · 2026Article
- Oxytocin modulation of the insular cortex: implications for social cognition and neurodevelopmental disorders.Frontiers in neural circuits · 2026Review
- Review
- Behavioral Assessment Reveals GnRH Immunocastration as a Better Alternative to Surgical Castration.Animals : an open access journal from MDPI · 2024Article
- Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior.Molecular psychiatry · 2024Article
- Artemisinin reduces PTSD-like symptoms, improves synaptic plasticity, and inhibits apoptosis in rats subjected to single prolonged stress.Frontiers in pharmacology · 2024Article
- IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system.Frontiers in behavioral neuroscience · 2023Review
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUntil 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.
methodsVPA-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.
resultsDeep 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.
conclusionsAutism-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.
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