Abstract
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.
Highlights
Autism spectrum disorder (ASD) is characterized by impairment of social communication, repetitive behavior and restrictive interest
To confirm whether valproic acid (VPA) mice were appropriate as a model of ASD under the experimental conditions of the present study, we performed the three-chambered social-approach test to evaluate the sociability and response to social novelty of VPA mice (Fig. 1A)
These results showed that the male VPA mice used in this study exhibited reduced social recognition
Summary
Autism spectrum disorder (ASD) is characterized by impairment of social communication, repetitive behavior and restrictive interest. 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. Autism spectrum disorder (ASD) is a developmental disorder characterized by disability of social communication, repetitive behavior, and restricted interests. Developmental Origins of Health and Disease (DOHaD) is a concept that entails that exposure to certain factors during the prenatal period may cause long-term side effects This paradigm helps to understand how risk factors present during fetal development contribute to the triggering of several disorders. LF reflects the sympathetic and parasympathetic nerve activities, HF reflects the parasympathetic nerve activity, and the LF/HF ratio reflects the sympathetic nerve activity
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