REDUCED NERVE GROWTH FACTOR LEVELS IN STRESS-RELATED BRAIN REGIONS OF FOLATE-DEFICIENT MICE

REDUCED NERVE GROWTH FACTOR LEVELS IN STRESS-RELATED BRAIN REGIONS OF FOLATE-DEFICIENT MICE
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DOI:
10.1016/j.neuroscience.2013.04.014
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发表时间:
2013-08-15
期刊:
影响因子:
3.3
通讯作者:
Hellweg, R.
Hellweg, R.
中科院分区:
医学3区
文献类型:
--
作者:
Eckart, S.;Hoertnag, H.;Hellweg, R.

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叶酸缺乏与神经退行性疾病和与压力有关的疾病,如中风、痴呆和抑郁症有关。神经营养因子神经生长因子(NGF)和神经营养因子-3 (NT-3)在应激相关疾病和神经退行性疾病中的作用近年来受到越来越多的关注。尿嘧啶错配参与实验性叶酸剥夺引起的神经精神功能障碍。然而,叶酸缺乏对脑组织中NGF和NT-3表达的影响尚未被研究。在2 × 2设计中,缺乏尿嘧啶- dna n -糖基酶(Ung(-/-))和野生型(Ung(+/+))对照的老年小鼠接受叶酸缺乏饮食和常规饮食三个月。与基因型无关,叶酸缺乏导致额叶皮层和杏仁核中NGF蛋白水平下降。在海马中,正常饮食的UNG(-/-)小鼠的NGF水平升高,但叶酸缺乏的情况下没有升高,而在UNG(+/+)小鼠中,叶酸剥夺不影响海马NGF含量。NT-3蛋白浓度不受基因型和叶酸缺乏的影响。总之,我们的研究结果表明,叶酸缺乏会影响额叶皮质、杏仁核和海马体中的NGF水平。在Ung(-/-)小鼠中,叶酸缺乏导致海马NGF含量降低,可能导致其焦虑和绝望样行为增强的表型以及选择性海马神经变性。(c) 2013 ibro。Elsevier Ltd.出版。版权所有。
Folate deficiency has been linked to neurodegenerative and stress-related diseases such as stroke, dementia and depression. The role of the neurotrophins nerve growth factor (NGF) and neurotrophin-3 (NT-3) in stress-related disorders and neurodegeneration has garnered increasing attention in recent years. Uracil misincorporation is involved in the neuropsychiatric dysfunction induced by experimental folate deprivation. However, the effects of folate deficiency on the expression of NGF and NT-3 in brain tissue have not yet been investigated. In a 2 x 2 design, aged mice lacking uracil-DNA N-glycosylase (Ung(-/-)) versus wild-type (Ung(+/+)) controls were subjected to a folate-deficient diet versus a regular diet for three months. Independent of genotype, folate deficiency led to decreased NGF protein levels in the frontal cortex and amygdala. In the hippocampus, NGF levels were increased in UNG(-/-) mice on the normal diet, but not under folate deficiency, while in UNG(+/+) mice, folate deprivation did not affect hippocampal NGF content. NT-3 protein concentrations were neither affected by genotype nor by folate deficiency. Altogether, the results of our study show that folate deficiency affects NGF levels in the frontal cortex, amygdala and hippocampus. The decrease in NGF content in the hippocampus in response to folate deficiency in Ung(-/-) mice may contribute to their phenotype of enhanced anxiety and despair-like behavior as well as to selective hippocampal neurodegeneration. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.