趋化因子与抑郁症关系的研究进展
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摘要
炎症反应是抑郁症的重要发病机制之一。近年来研究表明,许多抑郁症患者的相应脑区都存在炎症反应,而介导炎症反应的趋化因子在其中发挥着重要的作用。趋化因子也与抑郁症涉及的神经可塑性、单胺类神经递质减少及神经内分泌系统密切相关。该文对近年来趋化因子与抑郁症关系的研究进展进行简要综述,以期为深入了解和治疗抑郁症带来新的启示。
Inflammation is an important mechanism and etiology of depression. In recent years, researchers have demonstrated that many depression patients are with inflammatory reactions in the corresponding brain regions, and simultaneously chemokines play an important role in depression and inflammation. Meanwhile, in the course of depression, chemokines and their receptors are involved in neuroplasticity, the decrease of monoamine neurotransmitters and neuroendocrine system. In this review, in order to further understand and find better treatment of depression, we summarize the recent studies of the relationship between chemokines and depression disorder.
Inflammation is an important mechanism and etiology of depression. In recent years, researchers have demonstrated that many depression patients are with inflammatory reactions in the corresponding brain regions, and simultaneously chemokines play an important role in depression and inflammation. Meanwhile, in the course of depression, chemokines and their receptors are involved in neuroplasticity, the decrease of monoamine neurotransmitters and neuroendocrine system. In this review, in order to further understand and find better treatment of depression, we summarize the recent studies of the relationship between chemokines and depression disorder.
引文
[1] Whiteford H A,Degenhardt L,Rehm J,et al.Global burden of disease attributable to mental and substance use disorders:findings from the Global Burden of Disease Study 2010 [J].Lancet,2013,382(9904):1575-86.
[2] 王真真,陈乃宏.抑郁症与炎症[J].神经药理学报,2013,3(5):27-37.[2] Wang Z Z,Chen N H.Depression and inflammation[J].Acta Neuropharmacol,2013,3(5):27-37.
[3] Williams J L,Holman D W,Klein R S.Chemokines in the balance:maintenance of homeostasis and protection at CNS barriers [J].Front Cell Neurosci,2014,5(8):e154.
[4] Campbell S J,Meier U,Mardiguian S,et al.Sickness behaviour is induced by a peripheral CXC-chemokine also expressed in multiple sclerosis and EAE [J].Brain Behav Immun,2010,24(5):738-46.
[5] Girotti M,Donegan J J,Morilak D A.Chronic intermittent cold stress sensitizes neuro-immune reactivity in the rat brain [J].Psychoneuroendocrinology,2011,36(8):1164-74.
[6] Duan L,Zhang X D,Miao W Y,et al.PDGFRβ cells rapidly relay inflammatory signal from the circulatory system to neurons via chemokine CCL2 [J].Neuron,2018,100(1):183-200.
[7] Bolos M,Perea J R,Terreros-Roncal J,et al.Absence of microglial CX3CR1 impairs the synaptic integration of adult-born hippocampal granule neurons [J].Brain Behav Immun,2018,68:76-89.
[8] Corona A W,Huang Y,O’Connor J C,et al.Fractalkine receptor (CX3CR1) deficiency sensitizes mice to the behavioral changes induced by lipopolysaccharide [J].J Neuroinflammation,2010,7:93.
[9] Corona A W,Norden D M,Skendelas J P,et al.Indoleamine 2,3-dioxygenase inhibition attenuates lipopolysaccharide induced persistent microglial activation and depressive-like complications in fractalkine receptor (CX3CR1)-deficient mice [J].Brain Behav Immun,2013,31:134-42.
[10] Hellwig S,Brioschi S,Dieni S,et al.Altered microglia morphology and higher resilience to stress-induced depression-like behavior in CX3CR1-deficient mice [J].Brain Behav Immun,2016,55:126-37.
[11] Baune B T,Smith E,Reppermund S,et al.Inflammatory biomarkers predict depressive,but not anxiety symptoms during aging:the prospective sydney memory and aging study [J].Psychoneuroendocrinology,2012,37(9):1521-30.
[12] Simon N M,McNamara K,Chow C W,et al.A detailed examination of cytokine abnormalities in major depressive disorder [J].Eur Neuropsychopharmacol,2008,18(3):230-3.
[13] Lindqvist D,Janelidze S,Erhardt S,et al.CSF biomarkers in suicide attempters—a principal component analysis [J].Acta Psychiatr Scand,2011,124(1):52-61.
[14] van Zuiden M,Heijnen C J,van de Schoot R,et al.Cytokine production by leukocytes of military personnel with depressive symptoms after deployment to a combat-zone:a prospective,longitudinal study [J].PLoS One,2011,6(12):e29142.
[15] 姜懿纳,陈乃宏.CCL2/MCP-1在其相关疾病的机制研究 [J].中国药理学通报,2016,32(12):1634-8.[15] Jiang Y N,Chen N H.Mechanism of CCL2/MCP-1 in its relevant diseases [J].Chin Pharmacol Bull,2016,32(12):1634-8.
[16] Oglodek E A,Szota A,Just M J,et al.Comparison of chemokines (CCL-5 and SDF-1),chemokine receptors (CCR-5 and CXCR-4) and IL-6 levels in patients with different severities of depression [J].Pharmacol Rep,2014,66(5):920-6.
[17] Sakamoto Y,Koike K,Kiyama H,et al.Endotoxin activates a chemokinergic neuronal pathway in the hypothalamo-pituitary system [J].Endocrinology,1996,137(10):4503-6.
[18] Fernandez E J,Lolis E.Structure,function,and inhibition of chemokines [J].Annu Rev Pharmacol Toxicol,2002,42:469-99.
[19] Schwarting G A,Henion T R,Nugent J D,et al.Stromal cell-derived factor-1 (chemokine C-X-C motif ligand 12) and chemokine C-X-C motif receptor 4 are required for migration of gonadotropin-releasing hormone neurons to the forebrain [J].J Neurosci,2006,26(25):6834-40.
[20] Stuart M J,Corrigan F,Baune B T.Knockout of CXCR5 increases the population of immature neural cells and decreases proliferation in the hippocampal dentate gyrus [J].J.Neuroinflammation,2014,11:31.
[21] Xiao F,Xu J M,Jiang X H.CX3 chemokine receptor 1 deficiency leads to reduced dendritic complexity and delayed maturation of newborn neurons in the adult mouse hippocampus [J].Neural Regen Res,2015,10(5):772-7.
[22] Paolicelli R C,Bolasco G,Pagani F,et al.Synaptic pruning by microglia is necessary for normal brain development [J].Science,2011,333(6048):1456-8.
[23] Paolicelli R C,Bisht K,Tremblay M è.Fractalkine regulation of microglial physiology and consequences on the brain and behavior [J].Front Cell Neurosci,2014,8:129.
[24] Sheridan G K,Wdowicz A,Pickering M,et al.CX3CL1 is up-regulated in the rat hippocampus during memory-associated synaptic plasticity[J].Front Cell Neurosci,2014,8:233.
[25] Kettenmann H,Kirchhoff F,Verkhratsky A.Microglia:new roles for the synaptic stripper [J].Neuron,2013,77(1):10-8.
[2] 王真真,陈乃宏.抑郁症与炎症[J].神经药理学报,2013,3(5):27-37.[2] Wang Z Z,Chen N H.Depression and inflammation[J].Acta Neuropharmacol,2013,3(5):27-37.
[3] Williams J L,Holman D W,Klein R S.Chemokines in the balance:maintenance of homeostasis and protection at CNS barriers [J].Front Cell Neurosci,2014,5(8):e154.
[4] Campbell S J,Meier U,Mardiguian S,et al.Sickness behaviour is induced by a peripheral CXC-chemokine also expressed in multiple sclerosis and EAE [J].Brain Behav Immun,2010,24(5):738-46.
[5] Girotti M,Donegan J J,Morilak D A.Chronic intermittent cold stress sensitizes neuro-immune reactivity in the rat brain [J].Psychoneuroendocrinology,2011,36(8):1164-74.
[6] Duan L,Zhang X D,Miao W Y,et al.PDGFRβ cells rapidly relay inflammatory signal from the circulatory system to neurons via chemokine CCL2 [J].Neuron,2018,100(1):183-200.
[7] Bolos M,Perea J R,Terreros-Roncal J,et al.Absence of microglial CX3CR1 impairs the synaptic integration of adult-born hippocampal granule neurons [J].Brain Behav Immun,2018,68:76-89.
[8] Corona A W,Huang Y,O’Connor J C,et al.Fractalkine receptor (CX3CR1) deficiency sensitizes mice to the behavioral changes induced by lipopolysaccharide [J].J Neuroinflammation,2010,7:93.
[9] Corona A W,Norden D M,Skendelas J P,et al.Indoleamine 2,3-dioxygenase inhibition attenuates lipopolysaccharide induced persistent microglial activation and depressive-like complications in fractalkine receptor (CX3CR1)-deficient mice [J].Brain Behav Immun,2013,31:134-42.
[10] Hellwig S,Brioschi S,Dieni S,et al.Altered microglia morphology and higher resilience to stress-induced depression-like behavior in CX3CR1-deficient mice [J].Brain Behav Immun,2016,55:126-37.
[11] Baune B T,Smith E,Reppermund S,et al.Inflammatory biomarkers predict depressive,but not anxiety symptoms during aging:the prospective sydney memory and aging study [J].Psychoneuroendocrinology,2012,37(9):1521-30.
[12] Simon N M,McNamara K,Chow C W,et al.A detailed examination of cytokine abnormalities in major depressive disorder [J].Eur Neuropsychopharmacol,2008,18(3):230-3.
[13] Lindqvist D,Janelidze S,Erhardt S,et al.CSF biomarkers in suicide attempters—a principal component analysis [J].Acta Psychiatr Scand,2011,124(1):52-61.
[14] van Zuiden M,Heijnen C J,van de Schoot R,et al.Cytokine production by leukocytes of military personnel with depressive symptoms after deployment to a combat-zone:a prospective,longitudinal study [J].PLoS One,2011,6(12):e29142.
[15] 姜懿纳,陈乃宏.CCL2/MCP-1在其相关疾病的机制研究 [J].中国药理学通报,2016,32(12):1634-8.[15] Jiang Y N,Chen N H.Mechanism of CCL2/MCP-1 in its relevant diseases [J].Chin Pharmacol Bull,2016,32(12):1634-8.
[16] Oglodek E A,Szota A,Just M J,et al.Comparison of chemokines (CCL-5 and SDF-1),chemokine receptors (CCR-5 and CXCR-4) and IL-6 levels in patients with different severities of depression [J].Pharmacol Rep,2014,66(5):920-6.
[17] Sakamoto Y,Koike K,Kiyama H,et al.Endotoxin activates a chemokinergic neuronal pathway in the hypothalamo-pituitary system [J].Endocrinology,1996,137(10):4503-6.
[18] Fernandez E J,Lolis E.Structure,function,and inhibition of chemokines [J].Annu Rev Pharmacol Toxicol,2002,42:469-99.
[19] Schwarting G A,Henion T R,Nugent J D,et al.Stromal cell-derived factor-1 (chemokine C-X-C motif ligand 12) and chemokine C-X-C motif receptor 4 are required for migration of gonadotropin-releasing hormone neurons to the forebrain [J].J Neurosci,2006,26(25):6834-40.
[20] Stuart M J,Corrigan F,Baune B T.Knockout of CXCR5 increases the population of immature neural cells and decreases proliferation in the hippocampal dentate gyrus [J].J.Neuroinflammation,2014,11:31.
[21] Xiao F,Xu J M,Jiang X H.CX3 chemokine receptor 1 deficiency leads to reduced dendritic complexity and delayed maturation of newborn neurons in the adult mouse hippocampus [J].Neural Regen Res,2015,10(5):772-7.
[22] Paolicelli R C,Bolasco G,Pagani F,et al.Synaptic pruning by microglia is necessary for normal brain development [J].Science,2011,333(6048):1456-8.
[23] Paolicelli R C,Bisht K,Tremblay M è.Fractalkine regulation of microglial physiology and consequences on the brain and behavior [J].Front Cell Neurosci,2014,8:129.
[24] Sheridan G K,Wdowicz A,Pickering M,et al.CX3CL1 is up-regulated in the rat hippocampus during memory-associated synaptic plasticity[J].Front Cell Neurosci,2014,8:233.
[25] Kettenmann H,Kirchhoff F,Verkhratsky A.Microglia:new roles for the synaptic stripper [J].Neuron,2013,77(1):10-8.