Department of Nutrition, University of California Davis, Davis, California, USA.
Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany.
FASEB J. 2019 Feb;33(2):1681-1694. doi: 10.1096/fj.201701290RR. Epub 2018 Sep 10.
Osteopontin (OPN) is a pleiotropic protein and is abundantly present in milk. Its functions include immune modulation and cellular proliferation and differentiation. OPN is highly expressed in the brain. We investigated the effects of milk-derived OPN on brain development of mouse pups. Wild-type (WT) dams producing OPN milk and OPN knockout (KO) dams producing OPN milk nursed WT pups (OPN), yielding 2 pup treatment groups, OPN OPN and OPN OPN, for comparison. Preliminary studies supported use of this model by showing high concentrations of OPN in milk of WT dams and no OPN in milk of OPN KO dams, and production of similar amounts of milk by WT and KO dams. The ability of ingested milk OPN to enter the brain was revealed by appearance of orally gavaged [I]-labeled and antibody-probed milk OPN in brains of pups. Brain OPN mRNA levels were similar in both nursed groups, but the brain OPN protein level was significantly lower in the OPN OPN group at postnatal days 6 and 8. Behavior tests showed impaired memory and learning ability in OPN OPN pups. In addition, our study revealed increased expression of myelination-related proteins and elevated proliferation and differentiation of NG-2 glia into oligodendrocytes in the brain of OPN OPN pups, accompanied by increased activation of ERK-1/2 and PI3K/Akt signaling. We concluded that milk OPN can play an important role in brain development and behavior in infancy by promoting myelination.-Jiang, R., Prell, C., Lönnerdal, B. Milk osteopontin promotes brain development by up-regulating osteopontin in the brain in early life.
骨桥蛋白 (OPN) 是一种多功能蛋白，在牛奶中大量存在。它的功能包括免疫调节、细胞增殖和分化。OPN 在大脑中高度表达。我们研究了牛奶来源的 OPN 对小鼠幼仔大脑发育的影响。产生 OPN 牛奶的野生型 (WT) 母鼠和产生 OPN 牛奶的 OPN 敲除 (KO) 母鼠哺育 WT 幼仔 (OPN)，产生 2 个幼仔处理组，OPN OPN 和 OPN OPN，进行比较。初步研究支持使用该模型，结果表明 WT 母鼠牛奶中 OPN 浓度高，而 OPN KO 母鼠牛奶中无 OPN，WT 和 KO 母鼠产奶量相似。通过对用口服灌胃的 [I]-标记和抗体探测的牛奶 OPN 在幼仔大脑中的出现，揭示了摄入的牛奶 OPN 进入大脑的能力。两组被哺乳的幼仔大脑 OPN mRNA 水平相似，但在出生后第 6 和 8 天，OPN OPN 组的大脑 OPN 蛋白水平显著降低。行为测试显示 OPN OPN 幼仔的记忆和学习能力受损。此外，我们的研究还揭示了 OPN OPN 幼仔大脑中髓鞘形成相关蛋白表达增加，NG-2 神经胶质细胞增殖和分化为少突胶质细胞增加，并伴随着 ERK-1/2 和 PI3K/Akt 信号通路的激活增加。我们得出结论，牛奶 OPN 通过在婴儿期早期上调大脑中的 OPN，在大脑发育和行为中发挥重要作用。
