Functional and molecular characterization of a non-human primate model of autism spectrum disorder shows similarity with the human disease

Satoshi Watanabe (), Tohru Kurotani, Tomofumi Oga, Jun Noguchi, Risa Isoda, Akiko Nakagami, Kazuhisa Sakai, Keiko Nakagaki, Kayo Sumida, Kohei Hoshino, Koichi Saito, Izuru Miyawaki, Masayuki Sekiguchi, Keiji Wada, Takafumi Minamimoto and Noritaka Ichinohe ()
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Satoshi Watanabe: National Center of Neurology and Psychiatry
Tohru Kurotani: National Center of Neurology and Psychiatry
Tomofumi Oga: National Center of Neurology and Psychiatry
Jun Noguchi: National Center of Neurology and Psychiatry
Risa Isoda: National Center of Neurology and Psychiatry
Akiko Nakagami: National Center of Neurology and Psychiatry
Kazuhisa Sakai: National Center of Neurology and Psychiatry
Keiko Nakagaki: National Center of Neurology and Psychiatry
Kayo Sumida: Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Konohana-ku
Kohei Hoshino: Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., Konohana-ku
Koichi Saito: Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Konohana-ku
Izuru Miyawaki: Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., Konohana-ku
Masayuki Sekiguchi: National Center of Neurology and Psychiatry
Keiji Wada: National Center of Neurology and Psychiatry
Takafumi Minamimoto: National Institutes for Quantum and Radiological Science and Technology, Chiba
Noritaka Ichinohe: National Center of Neurology and Psychiatry

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Autism spectrum disorder (ASD) is a multifactorial disorder with characteristic synaptic and gene expression changes. Early intervention during childhood is thought to benefit prognosis. Here, we examined the changes in cortical synaptogenesis, synaptic function, and gene expression from birth to the juvenile stage in a marmoset model of ASD induced by valproic acid (VPA) treatment. Early postnatally, synaptogenesis was reduced in this model, while juvenile-age VPA-treated marmosets showed increased synaptogenesis, similar to observations in human tissue. During infancy, synaptic plasticity transiently increased and was associated with altered vocalization. Synaptogenesis-related genes were downregulated early postnatally. At three months of age, the differentially expressed genes were associated with circuit remodeling, similar to the expression changes observed in humans. In summary, we provide a functional and molecular characterization of a non-human primate model of ASD, highlighting its similarity to features observed in human ASD.

Date: 2021
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DOI: 10.1038/s41467-021-25487-6

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