Shigemori Tomoko, Sakai Atsushi, Takumi Toru, Itoh Yasuhiko, Suzuki Hidenori
Department of Pharmacology, Nippon Medical School, 2) Department of Pediatrics, Nippon Medical School.
J Nippon Med Sch. 2015;82(2):92-9. doi: 10.1272/jnms.82.92.
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.
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.
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.
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.
自闭症谱系障碍（ASD）是一种具有强大遗传基础的神经发育障碍。尽管焦虑是ASD中常见的主要精神疾病状况，但其潜在机制仍知之甚少。在患有ASD的个体中，有证据表明杏仁核存在结构异常，杏仁核是参与焦虑和社会行为的关键组成部分。小胶质细胞是参与神经发育过程的中枢神经系统驻留免疫细胞，据报道在ASD中也发生了改变。在本研究中，我们研究了小胶质细胞在ASD模型小鼠焦虑相关行为中的作用。
将具有与人类染色体15q11 - q13相对应的6.3 Mb父系重复（patDp/+）的小鼠用作ASD模型。使用免疫荧光法在杏仁核中检测小胶质细胞激活标志物离子钙结合衔接分子1（Iba1）。在新生和青春期的patDp/+小鼠中，研究了围产期用小胶质细胞调节剂米诺环素治疗对焦虑相关行为的影响。
在patDp/+小鼠中，出生后第7天基底外侧杏仁核中的Iba1减少，但在出生后第37 - 40天未减少。围产期用米诺环素治疗可恢复Iba1表达，并减少patDp/+青春期小鼠的焦虑相关行为。
基底外侧杏仁核中的围产期小胶质细胞可能在具有人类染色体15q11 - q13重复的ASD小鼠模型中观察到的焦虑中起致病作用。
