Endo Nozomi, Hiraishi Atsuo, Goto Sayaka, Nozu Hitoshi, Mannari-Sasagawa Takayo, Horii-Hayashi Noriko, Kitsuki Michiko, Okuda Mamiko, Makinodan Manabu, Nishi Mayumi
Department of Anatomy and Cell Biology, Nara Medical University, Kashihara, Japan.
Department of Pharmacology, School of Medicine, Hyogo Medical University, Nishinomiya, Japan.
Neuropsychopharmacol Rep. 2025 Mar;45(1):e12508. doi: 10.1002/npr2.12508. Epub 2024 Nov 28.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Some children with ASD show enhanced cortisol response to stress. BTBR T Itpr3/J (BTBR) mice, an ASD model, display behavior consistent with the three diagnostic categories of ASD and exhibit an exaggerated response to stress in adulthood. However, it remains unclear how basal corticosterone levels change and how the hypothalamic-pituitary-adrenal axis responds to stress during the early life stages in BTBR mice. In this study, we found that basal corticosterone levels showed characteristic changes, peaking at weaning during postnatal development in both BTBR and control C57BL/6J (B6J) mice. Furthermore, we observed higher corticosterone and corticotropin-releasing hormone levels in BTBR mice than in B6J mice following acute stress exposure during weaning; however, adrenocorticotropic hormone levels were lower in BTBR mice. Glucocorticoid receptor mRNA expression levels in the hippocampus and lateral septum after stress were higher in BTBR mice than in B6J mice. This study documented changes in corticosterone levels at baseline during postnatal development in mice and showed that BTBR mice exhibited disrupted stress responses at weaning.
自闭症谱系障碍（ASD）是一种神经发育障碍。一些患有ASD的儿童对应激的皮质醇反应增强。BTBR T Itpr3/J（BTBR）小鼠是一种ASD模型，其行为与ASD的三个诊断类别一致，并且在成年期对应激表现出过度反应。然而，尚不清楚BTBR小鼠在生命早期阶段基础皮质酮水平如何变化以及下丘脑-垂体-肾上腺轴对应激如何反应。在本研究中，我们发现基础皮质酮水平呈现特征性变化，在BTBR和对照C57BL/6J（B6J）小鼠出生后发育过程中的断奶期达到峰值。此外，我们观察到在断奶期急性应激暴露后，BTBR小鼠的皮质酮和促肾上腺皮质激素释放激素水平高于B6J小鼠；然而，BTBR小鼠的促肾上腺皮质激素水平较低。应激后，BTBR小鼠海马体和外侧隔区的糖皮质激素受体mRNA表达水平高于B6J小鼠。本研究记录了小鼠出生后发育过程中基线皮质酮水平的变化，并表明BTBR小鼠在断奶期表现出应激反应紊乱。
