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Suppressive effect of lactoferrin on behavioral abnormality in the maternally separated rats.

乳铁蛋白对母鼠分离大鼠行为异常的抑制作用。

基本信息

批准号：
17580256
负责人：
TAKEUCHI Takashi
金额：
$ 2.24万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17580256/
关键词：
Lactoferrin Maternal separation Opioid Catecholamine HPA-axis Nitric oxide

项目摘要

Lactoferrin (LF) is known as an iron-binding glycoprotein, especially contained in milk. We have shown that intra-duodenally administered bovine-LF (bLF) was absorbed from intestine and transported into blood circulation via receptor mediated system in adult rats. We found that a part of the intestinally absorbed bLF was reached to the brain passing through a blood-brain-barrier or a blood-cerebrospinal-barrier. In this project, we focused a suppressive effect of lactoferrin on the behavioral abnormalities related with maternally-separated stresses in rats.Newborn rats were separated individually from home cage and dam from a postnatal day (PND) 2 to PND 11. On the separating day, the newborn rats were separated for 30 min, 1 h, 2 hr and 5 h. Particular abnormalities in behavioral test (elevated plus-maze test) were observed in the 5 h separated rats. Pre-treatment with bLF (100 mg/kg) injection (ip) suppressed these abnormal behaviors. Interestingly, the strongest effect of bLF was recognized when the bLF was applied to the dam rats before the separation. These effects of bLF was blocked by pre-treatment with naloxone, opioid receptor antagonist, or L-NAME, nitric oxide synthase blocker. bLF also suppressed hypothalamus-pituitary-adrenal axis reaction. Plasma corticosterone elevation induced by foot-shock stress was significantly suppressed by bLF in the adult rats.These results suggest that bLF is one of the natural mediators in the stress reaction, via endogenous opioid system and nitric oxide production.

乳铁蛋白（LF）是一种铁结合糖蛋白，特别是在牛奶中。我们已经证明，牛LF（bLF）在成年大鼠体内从肠道吸收并通过受体介导系统转运到血液循环中。我们发现一部分脑内吸收的bLF通过血脑屏障或血脑屏障到达大脑。在这个项目中，我们集中了乳铁蛋白对行为异常的抑制作用与母亲分离的压力在rates.Newborn大鼠单独从家庭笼和母亲从出生后第2天（PND）PND 11。分离当天分别分离30 min、1 h、2 h和5 h。在分离5 h的大鼠中观察到行为试验（高架十字迷宫试验）的特殊异常。预处理bLF（100 mg/kg）注射（ip）抑制这些异常行为。有趣的是，当在分离前将bLF应用于母鼠时，bLF的作用最强。bLF的这些作用可被阿片受体拮抗剂纳洛酮或一氧化氮合酶阻断剂L-NAME阻断。bLF还能抑制下丘脑-垂体-肾上腺轴反应。bLF能显著抑制足电击应激引起的大鼠血浆皮质酮水平的升高，提示bLF是应激反应的天然介质之一，其作用机制可能与内源性阿片系统和一氧化氮的产生有关。