Department of Basic Research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan.
Department of Basic Research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan; Laboratory for Social Brain Studies, Research Institute of Molecular Medicine and Pathobiochemistry, and Department of Biochemistry, Krasnoyarsk State Medical University named after Prof. V. F. Voino-Yasentsky, Krasnoyarsk 660022, Russian Federation.
Physiol Behav. 2021 Jun 1;235:113395. doi: 10.1016/j.physbeh.2021.113395. Epub 2021 Mar 21.
Receptor for advanced glycation end-products (RAGE) is a pattern recognition molecule belonging to the immunoglobulin superfamily, and it plays a role in the remodeling of endothelial cells under pathological conditions. Recently, it was shown that RAGE is a binding protein for oxytocin (OT) and a transporter of OT to the brain on neurovascular endothelial cells via blood circulation. Deletion of the mouse RAGE gene, Ager (RAGE KO), induces hyperactivity in male mice. Impairment of pup care by mother RAGE KO mice after stress exposure results in the death of neonates 1-2 days after pup birth. Therefore, to understand the role of RAGE during the postpartum period, this study aims to examine parental behavior in female RAGE KO mice and ultrasonic vocalizations in pups. RAGE KO mothers without stress before delivery raised their pups and displayed hyperactivity at postpartum day (PPD) 3. KO dams showed impaired retrieval or interaction behavior after additional stress, such as body restraint stress or exposure to a novel environment, but such impaired behavior disappeared at PPD 7. Postnatal day 3 pups emitted ultrasonic vocalizations at >60 kHz as a part of the mother-pup relationship, but the number and category of calls by RAGE KO pups were significantly lower than wild-type pups. The results indicate that RAGE is important in the manifestation of normal parental behavior in dams and for receiving maternal care by mouse pups; moreover, brain OT recruited by RAGE plays a role in damping of signals of additional external stress and endogenous stress during the early postpartum period. Thus, RAGE-dependent OT may be critical for initiating and maintaining the normal mother-child relationship.
晚期糖基化终产物受体（RAGE）是一种属于免疫球蛋白超家族的模式识别分子，它在病理条件下的内皮细胞重塑中发挥作用。最近表明，RAGE 是催产素（OT）的结合蛋白，也是通过血液循环将 OT 转运到神经血管内皮细胞的脑内的转运蛋白。敲除小鼠 RAGE 基因（Ager，RAGE KO）会导致雄性小鼠过度活跃。应激暴露后母鼠 RAGE KO 损害了对幼崽的照顾，导致新生幼崽在出生后 1-2 天死亡。因此，为了了解产后 RAGE 的作用，本研究旨在检查雌性 RAGE KO 小鼠的亲代行为和幼崽的超声发声。分娩前无应激的 RAGE KO 母亲抚养幼崽，在产后第 3 天（PPD）表现出过度活跃。KO 母鼠在额外的应激后，如身体束缚应激或暴露于新环境中，表现出检索或互动行为受损，但这种受损行为在 PPD 7 时消失。产后第 3 天的幼崽发出>60 kHz 的超声发声，作为母婴关系的一部分，但 RAGE KO 幼崽的发声次数和类型明显低于野生型幼崽。结果表明，RAGE 对于母鼠表现出正常的亲代行为以及幼鼠接受母鼠照顾至关重要；此外，由 RAGE 募集的脑 OT 在产后早期阻尼额外外部应激和内源性应激的信号中发挥作用。因此，依赖 RAGE 的 OT 可能对启动和维持正常的母子关系至关重要。
