Cold-stress hormones (CSHs) stimulate thermogenesis and have direct neuroprotective effects on the brain. The obligatory receptor components of two new CSHs (irisin and growth differentiation factor-15 [GDF15]) were recently discovered. Irisin binds integrin-αV/β5 heterodimers while GDF-15 binds to the orphan receptor glial cell-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL). In addition, integrin-αV/β5 was just identified as the key receptor mediating Zika virus infection in the CNS. We measured integrin-αV, integrin-β5, and GFRAL protein levels across 78 high-quality human male/female brain tissues in infants, toddlers, preschoolers, adolescent, and adults—providing the most robust analysis to date on their levels in the human cortex and hippocampus. We report that integrin-αV was detected at all ages in the prefrontal cortex with levels greatest in adults. Integrin-αV was also detected in the hippocampus in all age groups. In contrast, integrin-β5 was detected in cortex and hippocampus largely restricted to infants. Co-expression of integrin-αV/β5 in the human infant hippocampus and cortex suggests the possibility that irisin has a more robust effect on the developing vs. the adult brain and may have implications for Zika virus infection in infants and young children.

冷应激激素 (CSH) 会刺激产热并对大脑具有直接的神经保护作用。最近发现了两种新 CSH（鸢尾素和生长分化因子-15 [GDF15]）的必需受体成分。鸢尾素结合整联蛋白-αV/β5 异二聚体，而 GDF-15 结合孤儿受体神经胶质细胞衍生的神经营养因子 (GDNF) 家族受体 α 样 (GFRAL)。此外，整合素-αV/β5 刚刚被确定为介导中枢神经系统寨卡病毒感染的关键受体。我们测量了婴儿、幼儿、学龄前儿童、青少年和成人的 78 个高质量人类男性/女性脑组织中的整合素-αV、整合素-β5 和 GFRAL 蛋白水平——提供了迄今为止最可靠的人类水平分析皮层和海马体。我们报告说，整合素-αV 在所有年龄段的前额叶皮层中都被检测到，在成年人中的水平最高。在所有年龄组的海马中也检测到整合素-αV。相比之下，在皮层和海马中检测到整合素-β5，主要限于婴儿。整合素-αV/β5 在人类婴儿海马体和皮质中的共表达表明，鸢尾素对发育中的大脑与成人大脑相比具有更强的影响，并且可能对婴儿和幼儿的寨卡病毒感染有影响。