TNF-α and its receptors modulate complex behaviours and neurotrophins in transgenic mice
TNF-α and its receptors modulate complex behaviours and neurotrophins in transgenic mice
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DOI：
10.1016/j.psyneuen.2013.09.010
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发表时间：
2013-12-01
影响因子：
3.7
通讯作者：
Baune, Bernhard T.
中科院分区：
文献类型：
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作者：
Camara, Marie Lou;Corrigan, Frances;Baune, Bernhard T.
肿瘤坏死因子-α（TNF-α）不仅在免疫中起重要作用，而且在中枢神经系统（CNS）的正常功能中也起重要作用。在生理水平上，研究表明TNF-α对维持突触缩放至关重要，从而影响学习和记忆形成，同时也在调节焦虑和抑郁的病理状态中发挥作用。TNF-α信号主要通过其两种受体，TNF-R1和TNF-R2，然而这些受体在TNF-α介导的行为表型中发挥的确切作用还有待确定。我们评估了TNF-/-，TNF-R1（-/-）和TNF-R2（-/-）小鼠抗C57 BL/6野生型（WT）12周龄的小鼠，以评估空间记忆和在巴恩斯迷宫（BM）和Y-迷宫中的学习的测量，以及在一系列测试中的其他行为，如探索、社会互动、焦虑和抑郁样行为。我们还测量了海马和前额叶皮质神经营养因子神经生长因子（NGF）和脑源性神经营养因子（BDNF）的水平，并使用免疫组织化学分析来测量齿状回内增殖细胞（Ki67）和未成熟神经元（DCX）的数量。我们已经表明，年轻的成年TNF-/-和TNF-R1（-/-）小鼠在BM和Y-迷宫中表现出学习和记忆障碍，而TNF-R2（-/-）小鼠在这些测试中表现出良好的记忆力但学习缓慢。与WT小鼠相比，TNF-/-和TNF-R2（-/-）小鼠也表现出焦虑样行为的减少。ELISA分析表明，TNF-/-和TNF-R2（-/-）小鼠有较低水平的神经生长因子相比，野生型mice. Conclusion：这些结果表明，虽然缺乏TNF-α可以减少小鼠的焦虑样行为，一定的基础水平的TNF-α所需的正常认知的发展。此外，我们的研究结果表明，TNF-R1和TNF-R2信号传导在正常的CNS功能中起作用，敲除任一受体都会损害巴恩斯迷宫上的认知。(C)2013爱思唯尔有限公司保留所有权利。
Tumour necrosis factor-alpha (TNF-alpha) plays an important role not only in immunity but also in the normal functioning of the central nervous system (CNS). At physiological levels, studies have shown TNF-alpha is essential to maintain synaptic scaling and thus influence learning and memory formation while also playing a role in modulating pathological states of anxiety and depression. TNF-alpha signals mainly through its two receptors, TNF-R1 and TNF-R2, however the exact role that these receptors play in TNF-alpha mediated behavioural phenotypes is yet to be determined.Methods: We have assessed TNF-/-, TNF-R1(-/-) and TNF-R2(-/-) mice against C57BL/6 wild-type (WT) mice from 12 weeks of age in order to evaluate measures of spatial memory and learning in the Barnes maze (BM) and Y-maze, as well as other behaviours such as exploration, social interaction, anxiety and depression-like behaviour in a battery of tests. We have also measured hippocampal and prefrontal cortex levels of the neurotrophins nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) as well as used immunohistochemical analyses to measure number of proliferating cells (Ki67) and immature neurons (DCX) within the dentate gyrus.Results: We have shown that young adult TNF-/- and TNF-R1(-/-) mice displayed impairments in learning and memory in the BM and Y-maze, while TNF-R2(-/-) mice showed good memory but slow learning in these tests. TNF-/- and TNF-R2(-/-) mice also demonstrated a decrease in anxiety likebehaviour compared to WT mice. ELISA analyses showed TNF-/- and TNF-R2(-/-) mice had lower levels of NGF compared to WT mice.Conclusion: These results indicate that while lack of TNF-alpha can decrease anxiety-like behaviour in mice, certain basal levels of TNF-alpha are required for the development of normal cognition. Furthermore our results suggest that both TNF-R1 and TNF-R2 signalling play a rote in normal CNS function, with knockout of either receptor impairing cognition on the Barnes maze. (C) 2013 Elsevier Ltd. All rights reserved.