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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and interest restricted to specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 h post-fertilization, rearing them to the adult stage in fish water. For the first time, an integrative approach combining behavioral analysis and neurotransmitters profile has been used for determining the effects of early-life exposure to VPA both in the larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. A neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the potential predictive validity of this model for ASD research.
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http://dx.doi.org/10.3390/ijms25147688 | DOI Listing |
Toxicol Lett
September 2025
Mammalian Embryology, Department of Life Science, Faculty of Science and Engineering, Kindai University 3-4-1, Kowake, Higashiosaka, Osaka 577-8501, Japan. Electronic address:
Autism spectrum disorder (ASD) is a developmental disability characterized by impaired social communication and repetitive behaviors, and environmental and genetic factors are involved in its onset. The use of the antiepileptic drug valproic acid (VPA) during pregnancy is associated with neural tube defects and developmental disorders in the fetus. In this study, we aimed to identify abnormalities in cortical morphogenesis owing to prenatal VPA exposure and to elucidate the abnormalities in brain function associated with these abnormalities, particularly by comparing multiple and single environments.
View Article and Find Full Text PDFPhysiol Behav
September 2025
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; Cognitive Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
The barrel cortex is a specialized region of the primary somatosensory cortex that processes tactile information from whiskers. This study investigates how tactile stimulation (TS) affects excitatory receptive fields and surrounds suppression in barrel cortex neurons of male and female autistic-like rats, using various whisker displacement protocols. The animals were categorized into control, Valproic acid pre-treated (Val), and Val-TS treatment groups.
View Article and Find Full Text PDFEpilepsy affects around 1% of the global population and often requires long-term treatment with antiseizure medications (ASMs). However, the current treatment strategy is based on clinical acumen and trial and error, resulting in only about 50% of patients remaining seizure-free for at least 12 months with first-line ASMs. Valproic acid (VPA) is a commonly prescribed first-line ASM, yet <50% of patients experience inadequate seizure control (ISC) or unacceptable adverse reactions (UARs), necessitating discontinuation.
View Article and Find Full Text PDFMed Chem
September 2025
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54124, Greece.
Introduction: Inflammation and oxidative stress are considered main pathophysiological factors for neuronal and cardiovascular diseases, also leading to the impairment of main cellular metabolic pathways. Promotion of hyperlipidemia is also the result of inflammatory and oxidative (ROS production) processes. Additionally, compounds of medicinal interest like valproic and caffeic acids and amino acids like proline and tyrosine have shown antiinflammatory and cellular protective potency.
View Article and Find Full Text PDFJ Neurosci
September 2025
Center for Neurodegenerative Disease Research, Dept. Pathology, Perelman School of Medicine at the University of Pennsylvania, 3 Maloney Bldg, 3600 Spruce St, Philadelphia, PA 19140, USA.
Neuronal hyperexcitability is a hallmark of amyotrophic lateral sclerosis (ALS) but its relationship with the TDP-43 aggregates that comprise the predominant pathology in over 90% of ALS cases remains unclear. Emerging evidence indicates that TDP-43 pathology induces neuronal hyperexcitability, which may contribute to excitotoxic neuronal death. To characterize TDP-43 mediated network excitability changes in a disease-relevant model, we performed in vivo continuous electroencephalography monitoring and ex vivo acute hippocampal slice electrophysiology in rNLS8 mice (males and females), which express human TDP-43 with a defective nuclear localization signal (hTDP-43ΔNLS).
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