The Effect of Anti-Inflammatory Dimethylmalonic Acid on the Neurobehavioral Phenotype of a Neonatal ASD Model Induced by Antiepileptic Valproic Acid
<b>Background</b>: Valproic acid (VPA) is a medication used to treat epilepsy, bipolar disorder, and migraine. If taken during pregnancy, it can cause neural tube defects (NTDs) and leads to offspring ASD behavioral phenotype. It has recently been found that early postnatal VPA exposure...
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2025-07-01
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| author | Xiuwen Zhou Xiaowen Xu Lili Li Yiming Jin Qing Wang Xinxin Wang Meifang Jin Hong Ni |
| author_facet | Xiuwen Zhou Xiaowen Xu Lili Li Yiming Jin Qing Wang Xinxin Wang Meifang Jin Hong Ni |
| author_sort | Xiuwen Zhou |
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| description | <b>Background</b>: Valproic acid (VPA) is a medication used to treat epilepsy, bipolar disorder, and migraine. If taken during pregnancy, it can cause neural tube defects (NTDs) and leads to offspring ASD behavioral phenotype. It has recently been found that early postnatal VPA exposure can also induce the ASD phenotype, but the details of model production and intervention still need further investigation. Dimethylmalonic acid (DMM), a competitive inhibitor of succinate dehydrogenase, blocks the key element succinate of OXPHOS, decreasing the secretion of anti-inflammatory cytokines and ROS production. However, it is still unclear whether DMM is involved in the repair of developmental brain injuries. <b>Objectives</b>: The aim of this study was to evaluate the intervention effect and optimal dosage of DMM on behavioral phenotypes using a neonatal mouse VPA autism model. <b>Methods</b>: This experiment consists of two parts. The first part observed the effects of different concentrations of VPA on the development and neurobehavioral phenotype of mice. The second part determined the intervention effect of DMM on a developmental VPA autism model and determined the optimal therapeutic dose. <b>Results</b>: We found that the 40 mg/mL concentration had a greater impact on the neural reflex damage in mice. Moreover, DMM treatment can partially improve the neurobehavioral damage in the VPA model, and 20 mg/kg has the best intervention effect. <b>Conclusions</b>: This study provides valuable model construction data for further exploring the mechanism of DMM treatment for an ASD phenotype induced by VPA exposure in neonates. |
| format | Article |
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| institution | DOAJ |
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| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-eea979b3ff204e77a7e347c76565bc122025-08-20T03:02:58ZengMDPI AGBiomedicines2227-90592025-07-01137176510.3390/biomedicines13071765The Effect of Anti-Inflammatory Dimethylmalonic Acid on the Neurobehavioral Phenotype of a Neonatal ASD Model Induced by Antiepileptic Valproic AcidXiuwen Zhou0Xiaowen Xu1Lili Li2Yiming Jin3Qing Wang4Xinxin Wang5Meifang Jin6Hong Ni7Department of Brain Science, Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou 215025, ChinaDepartment of Brain Science, Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou 215025, ChinaDepartment of Brain Science, Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou 215025, ChinaDepartment of Brain Science, Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou 215025, ChinaDepartment of Brain Science, Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou 215025, ChinaDepartment of Brain Science, Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou 215025, ChinaDepartment of Brain Science, Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou 215025, ChinaDepartment of Brain Science, Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou 215025, China<b>Background</b>: Valproic acid (VPA) is a medication used to treat epilepsy, bipolar disorder, and migraine. If taken during pregnancy, it can cause neural tube defects (NTDs) and leads to offspring ASD behavioral phenotype. It has recently been found that early postnatal VPA exposure can also induce the ASD phenotype, but the details of model production and intervention still need further investigation. Dimethylmalonic acid (DMM), a competitive inhibitor of succinate dehydrogenase, blocks the key element succinate of OXPHOS, decreasing the secretion of anti-inflammatory cytokines and ROS production. However, it is still unclear whether DMM is involved in the repair of developmental brain injuries. <b>Objectives</b>: The aim of this study was to evaluate the intervention effect and optimal dosage of DMM on behavioral phenotypes using a neonatal mouse VPA autism model. <b>Methods</b>: This experiment consists of two parts. The first part observed the effects of different concentrations of VPA on the development and neurobehavioral phenotype of mice. The second part determined the intervention effect of DMM on a developmental VPA autism model and determined the optimal therapeutic dose. <b>Results</b>: We found that the 40 mg/mL concentration had a greater impact on the neural reflex damage in mice. Moreover, DMM treatment can partially improve the neurobehavioral damage in the VPA model, and 20 mg/kg has the best intervention effect. <b>Conclusions</b>: This study provides valuable model construction data for further exploring the mechanism of DMM treatment for an ASD phenotype induced by VPA exposure in neonates.https://www.mdpi.com/2227-9059/13/7/1765dimethylmalonic acidvalproic acidautism spectrum disorderneonateneurobehavior |
| spellingShingle | Xiuwen Zhou Xiaowen Xu Lili Li Yiming Jin Qing Wang Xinxin Wang Meifang Jin Hong Ni The Effect of Anti-Inflammatory Dimethylmalonic Acid on the Neurobehavioral Phenotype of a Neonatal ASD Model Induced by Antiepileptic Valproic Acid Biomedicines dimethylmalonic acid valproic acid autism spectrum disorder neonate neurobehavior |
| title | The Effect of Anti-Inflammatory Dimethylmalonic Acid on the Neurobehavioral Phenotype of a Neonatal ASD Model Induced by Antiepileptic Valproic Acid |
| title_full | The Effect of Anti-Inflammatory Dimethylmalonic Acid on the Neurobehavioral Phenotype of a Neonatal ASD Model Induced by Antiepileptic Valproic Acid |
| title_fullStr | The Effect of Anti-Inflammatory Dimethylmalonic Acid on the Neurobehavioral Phenotype of a Neonatal ASD Model Induced by Antiepileptic Valproic Acid |
| title_full_unstemmed | The Effect of Anti-Inflammatory Dimethylmalonic Acid on the Neurobehavioral Phenotype of a Neonatal ASD Model Induced by Antiepileptic Valproic Acid |
| title_short | The Effect of Anti-Inflammatory Dimethylmalonic Acid on the Neurobehavioral Phenotype of a Neonatal ASD Model Induced by Antiepileptic Valproic Acid |
| title_sort | effect of anti inflammatory dimethylmalonic acid on the neurobehavioral phenotype of a neonatal asd model induced by antiepileptic valproic acid |
| topic | dimethylmalonic acid valproic acid autism spectrum disorder neonate neurobehavior |
| url | https://www.mdpi.com/2227-9059/13/7/1765 |
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