Mechano growth factor, a splice variant of IGF-1, promotes neurogenesis in the aging mouse brain.
Mechano growth factor, a splice variant of IGF-1, promotes neurogenesis in the aging mouse brain.
复制标题
DOI：
10.1186/s13041-017-0304-0
复制
发表时间：
2017-07-07
期刊：
影响因子：
3.6
通讯作者：
Windebank AJ
中科院分区：
文献类型：
--
作者：
Tang JJ;Podratz JL;Lange M;Scrable HJ;Jang MH;Windebank AJ
机械生长因子（MGF）是IGF-1的剪接变体，首次在骨骼肌中描述。MGF诱导肌肉细胞增殖以响应肌肉应激和损伤。在对照组小鼠中，我们发现MGF在大脑的神经源性区域中的内源性表达，并且这些水平随着年龄的增长而下降。为了更好地了解MGF在大脑中的作用，我们使用了从出生起就组成性过表达MGF的转基因小鼠。MGF过表达显著增加海马齿状回（DG）和室下区（SVG）BrdU+增殖细胞的数量。尽管MGF过表达增加了增殖阶段成年海马神经发生的总体速率，但并没有改变有丝分裂后成熟阶段神经元的分布。然后，我们使用乳糖操纵子系统有条件地过表达MGF在小鼠脑中开始在1，3和12个月的组织学和行为学观察在24个月的年龄。有条件的过度表达有一个增加的BrdU+增殖细胞和BrdU+分化成熟的神经元在嗅球在24个月时，过度表达诱导从1个月和3个月的年龄，但不是当开始在12个月。这与保留的嗅觉功能有关。在体外，MGF增加了从SVZ衍生的神经干细胞（NSCs）收获的神经球的大小和数量。这些发现表明，MGF过表达增加神经前体细胞的数量，促进神经发生，但不改变成年新生神经元在有丝分裂后阶段的分布。保持年轻的MGF水平可能在逆转与年龄相关的神经元丢失和脑功能障碍方面很重要。本文的在线版本（doi：10.1186/s13041-017-0304-0）包含补充材料，可供授权用户使用。
Mechano growth factor (MGF) is a splice variant of IGF-1 first described in skeletal muscle. MGF induces muscle cell proliferation in response to muscle stress and injury. In control mice we found endogenous expression of MGF in neurogenic areas of the brain and these levels declined with age. To better understand the role of MGF in the brain, we used transgenic mice that constitutively overexpressed MGF from birth. MGF overexpression significantly increased the number of BrdU+ proliferative cells in the dentate gyrus (DG) of the hippocampus and subventricular zone (SVG). Although MGF overexpression increased the overall rate of adult hippocampal neurogenesis at the proliferation stage it did not alter the distribution of neurons at post-mitotic maturation stages. We then used the lac-operon system to conditionally overexpress MGF in the mouse brain beginning at 1, 3 and 12 months with histological and behavioral observation at 24 months of age. With conditional overexpression there was an increase of BrdU+ proliferating cells and BrdU+ differentiated mature neurons in the olfactory bulbs at 24 months when overexpression was induced from 1 and 3 months of age but not when started at 12 months. This was associated with preserved olfactory function. In vitro, MGF increased the size and number of neurospheres harvested from SVZ-derived neural stem cells (NSCs). These findings indicate that MGF overexpression increases the number of neural progenitor cells and promotes neurogenesis but does not alter the distribution of adult newborn neurons at post-mitotic stages. Maintaining youthful levels of MGF may be important in reversing age-related neuronal loss and brain dysfunction. The online version of this article (doi:10.1186/s13041-017-0304-0) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
2.5
作者：
Brown, JP;Couillard-Després, S;Kuhn, HG
通讯作者：
Kuhn, HG
影响因子：
3.5
作者：
Gago, N;Avellana-Adalid, V;Schumacher, M
通讯作者：
Schumacher, M
DOI：
10.18632/aging.100446
发表时间：
2012-03
期刊：
Aging
影响因子：
--
作者：
Artegiani B;Calegari F
通讯作者：
Calegari F
DOI：
10.1007/978-1-59745-019-5_18
发表时间：
2010-01-01
期刊：
MOUSE CELL CULTURE: METHODS AND PROTOCOLS
影响因子：
--
作者：
Ahlenius, Henrik;Kokaia, Zaal
通讯作者：
Kokaia, Zaal
DOI：
10.1073/pnas.96.13.7526
发表时间：
1999-06-22
影响因子：
11.1
作者：
Lim, DA;Alvarez-Buylla, A
通讯作者：
Alvarez-Buylla, A