TY - JOUR
T1 - Alterations in the autonomic nerve activities of prenatal autism model mice treated with valproic acid at different developmental stages
AU - Kasahara, Yoshiyuki
AU - Yoshida, Chihiro
AU - Nakanishi, Kana
AU - Fukase, Miyabi
AU - Suzuki, Arisa
AU - Kimura, Yoshitaka
N1 - Funding Information:
We thank Mr. Kunihiro Koide, Ms. Shizu Shoji and Ms. Chie Yoshida for assistance and technical advice, Ms. Namareq Widatalla for English proofreading, and Dr. Yuji Takano, Dr. Masatoshi Ukezono and Dr. Ahsan Khan-doker for their helpful advice and discussion. The work in this paper has been supported by RIKEN Healthcare and Medical Data Platform Project, the Creative Interdisciplinary Research Project of Frontier Research Institute for Interdisciplinary Science, Tohoku University, and the funding for basic medical research by Shiguredo Inc.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Autism spectrum disorder (ASD) is characterized by impairment of social communication, repetitive behavior and restrictive interest. The risk of ASD is strongly associated with the prenatal period; for instance, the administration of valproic acid (VPA) to pregnant mothers increases risk of ASD in the child. Patients with ASD often exhibit an alteration in the autonomic nervous system. In this study, we assessed the autonomic nervous activity at each prenatal developmental stage of model mice of ASD treated with VPA, to clarify the relationship between timing of exposure and ASD symptoms. The assessment of the autonomic nervous activity was performed based on the analysis of electrocardiography data collected from fetal and adult mice. Interestingly, VPA model mouse fetuses exhibited a significantly lower activity of the sympathetic nervous system. In contrast, sympathetic nervous activity at P0 was significantly higher. In adult VPA model mice, the parasympathetic activity of female VPA mice was suppressed. Moreover, female VPA mice showed reduced the parasympathetic activity after exposure to restraint stress. These results suggest that the autonomic nervous activity of VPA model mice was altered from the fetal stage, and that the assessment of autonomic nervous activities at an early developmental stage could be useful for the understanding of ASD.
AB - Autism spectrum disorder (ASD) is characterized by impairment of social communication, repetitive behavior and restrictive interest. The risk of ASD is strongly associated with the prenatal period; for instance, the administration of valproic acid (VPA) to pregnant mothers increases risk of ASD in the child. Patients with ASD often exhibit an alteration in the autonomic nervous system. In this study, we assessed the autonomic nervous activity at each prenatal developmental stage of model mice of ASD treated with VPA, to clarify the relationship between timing of exposure and ASD symptoms. The assessment of the autonomic nervous activity was performed based on the analysis of electrocardiography data collected from fetal and adult mice. Interestingly, VPA model mouse fetuses exhibited a significantly lower activity of the sympathetic nervous system. In contrast, sympathetic nervous activity at P0 was significantly higher. In adult VPA model mice, the parasympathetic activity of female VPA mice was suppressed. Moreover, female VPA mice showed reduced the parasympathetic activity after exposure to restraint stress. These results suggest that the autonomic nervous activity of VPA model mice was altered from the fetal stage, and that the assessment of autonomic nervous activities at an early developmental stage could be useful for the understanding of ASD.
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U2 - 10.1038/s41598-020-74662-0
DO - 10.1038/s41598-020-74662-0
M3 - Article
C2 - 33082409
AN - SCOPUS:85093098823
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 17722
ER -