Valproate-induced murine autism spectrum disorder is associated with dysfunction of amygdala parvalbumin interneurons and downregulation of AMPK/SIRT1/PGC1α signaling

Zahedi, Elham; Sadr, Seyed Shahabeddin; Sanaeierad, Ashkan; Roghani, Mehrdad

doi:10.1007/s11011-023-01227-1

Cited by 8 publications

(2 citation statements)

References 51 publications

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“…On the other hand, murine autism models have shown that VPA, by disrupting the AMPK/SIRT1/PGC1α signaling pathway, causes a dysfunction in the amygdala's interneurons accompanied by elevated ROS and caspase 3, neuroinflammation, and eventual manifestation of ASD [129]. In another murine model, it was shown that VPA upregulates miR134-5p, similar to what is observed in ASD.…”

Section: Vpa and Asdmentioning

confidence: 74%

Roles of Epigenetics and Glial Cells in Drug-Induced Autism Spectrum Disorder

Csoka,

El Kouhen,

Bennani

et al. 2024

Biomolecules

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by severe deficits in social communication and interaction, repetitive movements, abnormal focusing on objects, or activity that can significantly affect the quality of life of the afflicted. Neuronal and glial cells have been implicated. It has a genetic component but can also be triggered by environmental factors or drugs. For example, prenatal exposure to valproic acid or acetaminophen, or ingestion of propionic acid, can increase the risk of ASD. Recently, epigenetic influences on ASD have come to the forefront of investigations on the etiology, prevention, and treatment of this disorder. Epigenetics refers to DNA modifications that alter gene expression without making any changes to the DNA sequence. Although an increasing number of pharmaceuticals and environmental chemicals are being implicated in the etiology of ASD, here, we specifically focus on the molecular influences of the abovementioned chemicals on epigenetic alterations in neuronal and glial cells and their potential connection to ASD. We conclude that a better understanding of these phenomena can lead to more effective interventions in ASD.

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Section: Vpa and Asdmentioning

confidence: 74%

Roles of Epigenetics and Glial Cells in Drug-Induced Autism Spectrum Disorder

Csoka,

El Kouhen,

Bennani

et al. 2024

Biomolecules

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“…At the same time, mice in the VPA and the control groups were daily administered with normal saline via intragastric administration in an equivalent dose format. Following the protocol established by Zahedi et al, on embryonic day 12.5, pregnant mice in the VPA and AGM intervention groups received an intraperitoneal injection of 600 mg/kg VPA (Guimaraes‐Souza et al, 2019; Zahedi et al, 2023). The pregnant mice in the control group received equal amounts of normal saline daily during pregnancy.…”

Section: Methodsmentioning

confidence: 99%

The prenatal use of agmatine prevents social behavior deficits in VPA‐exposed mice by activating the ERK/CREB/BDNF signaling pathway

Chen,

Xu,

Zhao

et al. 2024

Birth Defects Research

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BackgroundAccording to reports, prenatal exposure to valproic acid can induce autism spectrum disorder (ASD)‐like symptoms in both humans and rodents. However, the exact cause and therapeutic method of ASD is not fully understood. Agmatine (AGM) is known for its neuroprotective effects, and this study aims to explore whether giving agmatine hydrochloride before birth can prevent autism‐like behaviors in mouse offspring exposed prenatally to valproic acid.MethodsIn this study, we investigated the effects of AGM prenatally on valproate (VPA)‐exposed mice. We established a mouse model of ASD by prenatally administering VPA. From birth to weaning, we evaluated mouse behavior using the marble burying test, open‐field test, and three‐chamber social interaction test on male offspring.ResultsThe results showed prenatal use of AGM relieved anxiety and hyperactivity behaviors as well as ameliorated sociability of VPA‐exposed mice in the marble burying test, open‐field test, and three‐chamber social interaction test, and this protective effect might be attributed to the activation of the ERK/CREB/BDNF signaling pathway.ConclusionTherefore, AGM can effectively reduce the likelihood of offspring developing autism to a certain extent when exposed to VPA during pregnancy, serving as a potential therapeutic drug.

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