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Altered Microglia in the Amygdala Are Involved in Anxiety-related Behaviors of a Copy Number Variation Mouse Model of Autism
1Department of Pharmacology, Nippon Medical School
2Department of Pediatrics, Nippon Medical School
3RIKEN Brain Science Institute
Background and Purpose: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic basis. Although anxiety is a common major psychiatric condition in ASD, the underlying mechanisms of the anxiety are poorly understood. In individuals with ASD, evidence indicates a structural abnormality in the amygdala, a key component involved in anxiety and social behavior. Microglia, which are central nervous system-resident immune cells implicated in neurodevelopmental processes, are also reportedly altered in ASD. In the present study, we examined the involvement of microglia in the anxiety-related behaviors of ASD model mouse.
Methods: Mice that have a 6.3-Mb paternal duplication (patDp/+) corresponding to human chromosome 15q11-q13 were used as an ASD model. Iba1, a microglial activation marker, was examined in the amygdala using immunofluorescence. Effects of perinatal treatment with minocycline, a microglial modulator, on anxiety-related behaviors were examined in neonatal and adolescent patDp/+ mice.
Results: In patDp/+ mice, Iba1 was decreased in the basolateral amygdala at postnatal day 7, but not at postnatal days 37-40. Perinatal treatment with minocycline restored the Iba1 expression and reduced anxiety-related behaviors in patDp/+ adolescent mice.
Conclusions: Perinatal microglia in the basolateral amygdala may play a pathogenic role in the anxiety observed in a mouse model of ASD with duplication of human chromosome 15q11-q13.
J Nippon Med Sch 2015; 82: 92-99
Keywords
amygdala, anxiety, autism spectrum disorder, microglia, minocycline
Correspondence to
Hidenori Suzuki, MD, PhD, Department of Pharmacology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
hsuzuki@nms.ac.jp
Received, December 22, 2014
Accepted, January 6, 2015