The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism
Abstract
Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. Interestingly, our previous study involving the valproic acid animal model of autism (VPA animal model) has demonstrated excitatory-inhibitory imbalance (E/I imbalance) due to enhanced differentiation of glutamatergic neurons and reduced GABAergic neurons. Here, we investigated the potential of agmatine, an endogenous NMDA receptor antagonist, as a novel therapeutic candidate in ameliorating ASD symptoms by modulating E/I imbalance using the VPA animal model. We observed that a single treatment of agmatine rescued the impaired social behaviors as well as hyperactive and repetitive behaviors in the VPA animal model. We also observed that agmatine treatment rescued the overly activated ERK1/2 signaling in the prefrontal cortex and hippocampus of VPA animal models, possibly, by modulating over-excitability due to enhanced excitatory neural circuit. Taken together, our results have provided experimental evidence suggesting a possible therapeutic role of agmatine in ameliorating ASD-like symptoms in the VPA animal model of ASD.
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“Accordingly, in rodents, VPA administration during gestation leads to ASD-like behaviors (notably social deficits) in offspring (Kim et al., 2017).”
From Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder (2019) · cites this paper as Kim et al., 2017
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Metadata
- Authors
- Kim, J.-W., Seung, H., Kim, K. C., Gonzales, E. L. T., Oh, H. A., Yang, S. M., Ko, M. J., Han, S.-H., Banerjee, S., & Shin, C. Y.
- Affiliations
- Konkuk University (KR)
- National Brain Research Centre (IN)
- Corresponding author
- Shin, Chan Young
- ORCID
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 113
- Issue
- Pt A
- Pages
- 71-81
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2519436935
- Cited by
- 102
- References
- 65
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 13 · 2023: 8 · 2022: 14 · 2021: 10 · 2020: 11 · 2019: 11 · 2018: 13 · 2017: 6
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea
- Korea government (2014R1A2A2A01003079, 2016R1A5A2012284)
- Korea Health industry Development Institute
- Ministry of Health & Welfare, Republic of Korea (HI12C0021)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- agmatine, autism spectrum disorder, excitatory-inhibitory imbalance, NMDA receptor antagonists, social behavior deficits, repetitive behavior, hyperactivity, ERK signaling, prefrontal cortex, hippocampus, glutamatergic neurons, GABAergic neurons, autism treatment
- MeSH terms
- Autism Spectrum Disorder, Agmatine, Animals, Disease Models, Animal, Grooming, Hippocampus, Hyperkinesis, Male, Mice, Transgenic, Neurons, Seizures, Social Behavior, Valproic Acid, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Prefrontal Cortex, MAP Kinase Signaling System, Mice, Rats, Neural Stem Cells, Primary Cell Culture
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