Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice
Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice
复制标题
DOI：
10.1046/j.1471-4159.2002.01085.x
复制
发表时间：
2002-09-01
影响因子：
4.7
通讯作者：
Mattson, MP
中科院分区：
文献类型：
--
作者：
Lee, J;Duan, W;Mattson, MP
为了确定脑源性神经营养因子（BDNF）在饮食限制（DR）导致的海马神经发生增强中的作用，我们将杂合BDNF敲除（BDNF +/-）小鼠和野生型小鼠在饮食限制（DR）或随意（AL）饮食中维持3个月。然后给小鼠注射溴脱氧尿嘧啶（BrdU）， 1天或4周后处死。BDNF +/-小鼠海马区神经元中BDNF蛋白水平降低，DR使野生型小鼠海马区神经元中BDNF蛋白水平升高，BDNF +/-小鼠海马区神经元中BDNF蛋白水平升高。在注射BrdU 1天后，维持AL饮食的BDNF +/-小鼠海马齿状回中BrdU标记的细胞数量显著减少，表明BDNF信号传导对神经干细胞的增殖很重要。DR对野生型或BDNF +/-小鼠的神经干细胞增殖无影响。BrdU注射4周后，在AL或DR饮食中维持BDNF +/-小鼠中，存活的标记细胞数量减少。DR显著提高了野生型小鼠新生细胞的存活率，也提高了BDNF +/-小鼠的存活率，尽管程度较低。大多数brdu标记的齿状回细胞在4周的时间点表现出神经元表型。BDNF +/-小鼠神经发生的减少与齿状回体积的显著减少有关。上述结果提示，BDNF在调节成年小鼠齿状回神经发生的基础水平中发挥重要作用，并通过促进新生神经元的存活参与DR诱导的神经发生的增强。
To determine the role of brain-derived neurotrophic factor (BDNF) in the enhancement of hippocampal neurogenesis resulting from dietary restriction (DR), heterozygous BDNF knockout (BDNF +/-) mice and wild-type mice were maintained for 3 months on DR or ad libitum (AL) diets. Mice were then injected with bromodeoxyuridine (BrdU) and killed either 1 day or 4 weeks later. Levels of BDNF protein in neurons throughout the hippocampus were decreased in BDNF +/- mice, but were increased by DR in wild-type mice and to a lesser amount in BDNF +/- mice. One day after BrdU injection the number of BrdU-labeled cells in the dentate gyrus of the hippocampus was significantly decreased in BDNF +/- mice maintained on the AL diet, suggesting that BDNF signaling is important for proliferation of neural stem cells. DR had no effect on the proliferation of neural stem cells in wild-type or BDNF +/- mice. Four weeks after BrdU injection, numbers of surviving labeled cells were decreased in BDNF +/- mice maintained on either AL or DR diets. DR significantly improved survival of newly generated cells in wild-type mice, and also improved their survival in BDNF +/- mice, albeit to a lesser extent. The majority of BrdU-labeled cells in the dentate gyrus exhibited a neuronal phenotype at the 4-week time point. The reduced neurogenesis in BDNF +/- mice was associated with a significant reduction in the volume of the dentate gyrus. These findings suggest that BDNF plays an important role in the regulation of the basal level of neurogenesis in dentate gyrus of adult mice, and that by promoting the survival of newly generated neurons BDNF contributes to the enhancement of neurogenesis induced by DR.