Immune modulation of learning, memory, neural plasticity and neurogenesis
Immune modulation of learning, memory, neural plasticity and neurogenesis
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DOI：
10.1016/j.bbi.2010.10.015
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发表时间：
2011-02-01
影响因子：
15.1
通讯作者：
Goshen, Inbal
中科院分区：
文献类型：
--
作者：
Yirmiya, Raz;Goshen, Inbal
在过去的二十年里，越来越明显的是，免疫系统在调节学习、记忆和神经可塑性方面发挥着核心作用。在正常静止状态下，免疫机制被环境/心理刺激激活，正向调节神经回路重塑，促进记忆巩固、海马长时程增强（LTP）和神经发生。免疫系统的这些有益作用是由具有免疫功能的脑细胞（特别是小胶质细胞和星形胶质细胞）、外周免疫细胞（特别是 T 细胞和巨噬细胞）、神经元和神经前体细胞之间复杂的相互作用介导的。这些相互作用涉及非神经元细胞对经典神经递质（例如谷氨酸和单胺）和激素（例如糖皮质激素）的反应，以及神经元和神经胶质细胞对低水平炎症细胞因子（例如白细胞介素（IL）-1、IL-6和TNF α）以及其他介质（例如前列腺素和神经营养素）的分泌和反应。在免疫系统因感染或损伤以及严重或慢性应激条件而强烈激活的情况下，神经胶质细胞和其他脑免疫细胞会改变其形态和功能，并分泌高水平的促炎细胞因子和前列腺素。这些炎症介质的产生破坏了免疫过程的神经生理作用所需的微妙平衡，并对记忆、神经可塑性和神经发生产生直接的有害影响。这些效应是由炎症引起的神经元过度兴奋和肾上腺皮质刺激介导的，随后神经营养蛋白和其他可塑性相关分子的产生减少，促进与正常衰老以及神经退行性和神经精神疾病相关的多种形式的神经病理学。 (C) 2010 Elsevier Inc. 保留所有权利。
Over the past two decades it became evident that the immune system plays a central role in modulating learning, memory and neural plasticity. Under normal quiescent conditions, immune mechanisms are activated by environmental/psychological stimuli and positively regulate the remodeling of neural circuits, promoting memory consolidation, hippocampal long-term potentiation (LTP) and neurogenesis. These beneficial effects of the immune system are mediated by complex interactions among brain cells with immune functions (particularly microglia and astrocytes), peripheral immune cells (particularly T cells and macrophages), neurons, and neural precursor cells. These interactions involve the responsiveness of non-neuronal cells to classical neurotransmitters (e.g., glutamate and monoamines) and hormones (e.g., glucocorticoids), as well as the secretion and responsiveness of neurons and glia to low levels of inflammatory cytokines, such as interleukin (IL)-1, IL-6, and TNF alpha, as well as other mediators, such as prostaglandins and neurotrophins. In conditions under which the immune system is strongly activated by infection or injury, as well as by severe or chronic stressful conditions, glia and other brain immune cells change their morphology and functioning and secrete high levels of pro-inflammatory cytokines and prostaglandins. The production of these inflammatory mediators disrupts the delicate balance needed for the neurophysiological actions of immune processes and produces direct detrimental effects on memory, neural plasticity and neurogenesis. These effects are mediated by inflammation-induced neuronal hyper-excitability and adrenocortical stimulation, followed by reduced production of neurotrophins and other plasticity-related molecules, facilitating many forms of neuropathology associated with normal aging as well as neurodegenerative and neuropsychiatric diseases. (C) 2010 Elsevier Inc. All rights reserved.