Sadakata Mizuki, Fujii Kazuki, Kaneko Ryosuke, Hosoya Emi, Sugimoto Hisako, Kawabata-Iwakawa Reika, Kasamatsu Tetsuhiro, Hongo Shoko, Koshidaka Yumie, Takase Akinori, Iijima Takatoshi, Takao Keizo, Sadakata Tetsushi
Education and Research Support Center, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
Department of Behavioral Physiology, Faculty of Medicine, University of Toyama, Toyama, 930-0194, Japan.
J Neuroinflammation. 2024 May 2;21(1):114. doi: 10.1186/s12974-024-03100-z.
Maternal immunoglobulin (Ig)G is present in breast milk and has been shown to contribute to the development of the immune system in infants. In contrast, maternal IgG has no known effect on early childhood brain development. We found maternal IgG immunoreactivity in microglia, which are resident macrophages of the central nervous system of the pup brain, peaking at postnatal one week. Strong IgG immunoreactivity was observed in microglia in the corpus callosum and cerebellar white matter. IgG stimulation of primary cultured microglia activated the type I interferon feedback loop by Syk. Analysis of neonatal Fc receptor knockout (FcRn KO) mice that could not take up IgG from their mothers revealed abnormalities in the proliferation and/or survival of microglia, oligodendrocytes, and some types of interneurons. Moreover, FcRn KO mice also exhibited abnormalities in social behavior and lower locomotor activity in their home cages. Thus, changes in the mother-derived IgG levels affect brain development in offsprings.
母体免疫球蛋白(Ig)G存在于母乳中,并且已被证明有助于婴儿免疫系统的发育。相比之下,母体IgG对幼儿大脑发育尚无已知影响。我们在小胶质细胞中发现了母体IgG免疫反应性,小胶质细胞是幼崽大脑中枢神经系统中的常驻巨噬细胞,在出生后一周达到峰值。在胼胝体和小脑白质的小胶质细胞中观察到强烈的IgG免疫反应性。IgG对原代培养的小胶质细胞的刺激通过Syk激活了I型干扰素反馈回路。对无法从母亲那里摄取IgG的新生Fc受体敲除(FcRn KO)小鼠的分析显示,小胶质细胞、少突胶质细胞和某些类型的中间神经元的增殖和/或存活存在异常。此外,FcRn KO小鼠在社交行为方面也表现出异常,并且在其饲养笼中的运动活动较低。因此,母体来源的IgG水平的变化会影响后代的大脑发育。