神经免疫系统对学习、记忆的影响

doi:10.16098/j.issn.0529-1356.2018.04.022

摘要/Abstract

摘要：

神经系统和免疫系统是维持机体内平衡的两个主要控制系统，具有双向调节作用。神经系统通过神经、内分泌途径，释放各种细胞因子、递质及神经肽调节机体的免疫反应过程；而免疫系统产生的免疫调节物或神经活性物质又可以调节神经系统的功能。神经-免疫系统的交互作用对促进神经系统正常功能的维持和发育具有重要作用。我们就大脑内部的免疫细胞即小胶质细胞、炎症细胞因子即白细胞介素（IL）-1β（IL-1β）、IL-6 和肿瘤坏死因子、Toll 样受体以及外周免疫系统在学习记忆以及调节突触传递、神经发生等功能方面的研究进行综述。

关键词: 小胶质细胞, 炎性细胞因子, 海马, 神经发生

Abstract:

Nervous system and immune system are two main controlling systems for sustaining internal balance of the body, which can mutual regulate each other. The nervous system regulates the immune response of the organism through the nervous and endocrine pathways by releases various cytokines, transmitters and neuropeptides. In turn, immune modulator or neural active substances produced by immune system can regulate the functions of the nervous system. The interaction between the nervous system and the immune system plays an important role in the maintenance and development of the normal function of the nervous system. We review research progress of roles of the immune system include microglia, inflammatory cytokines, especially interleukin (IL)-1β, IL-6, tumor necrosis factor and Toll-like receptors, and peripheral immune system in the normal hippocampal functions such as learning and memory, synaptic transmission, and nerogenesis.

Key words: Microglia, Inflammatory cytokine, Hippocampus, Neurogenesis

丁艳平金毅然白玉洁潘子彦邵宝平. 神经免疫系统对学习、记忆的影响[J]. 解剖学报, 2018, 49(4): 543-548.

DING Yan-ping JIN Yi-ran BAI Yu-jie PAN Zi-yan SHAO Bao-ping. Regulation of neuroimmune system on learning and memory[J]. Acta Anatomica Sinica, 2018, 49(4): 543-548.

参考文献

［1］ Lécuyer MA，Kebir H，Prat A. Glial influences on BBB functions and molecular players in immune cell trafficking ［J］. Biochim Biophys Acta，2016，1862(3)：472-482.

［2］ Zhu ChG. The relationship between neuro-immuno-endocrine network and epileptogenesis ［J］. Acra Anatomica Sinica，2002,33 (3)：321-324. (in Chinese)

朱长庚. 神经-免疫-内分泌网络与癫痫发病机理的关系［J］. 解剖学报，2002, 33(3)：321-324.

［3］ Yirmiya R，Goshen Ⅰ. Immune modulation of learning，memory，neural plasticity and neurogenesis ［J］. Brain Behav Immun，2011，25(2)：181-213.

［4］ Elmore MR， Najafi AR， Koike MA，et al. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability，unmasking a microglia progenitor cell in the adult brain ［J］. Neuron,2014，82(2):380-397.

［5］ Swinnen N，Smolders S，Avila A，et al. Complex invasion pattern of the cerebral cortex bymicroglial cells during development of the mouse embryo ［J］. Glia，2013，61(2)：150-163.

［6］ Sierra A，Beccari S，Diaz-Aparicio Ⅰ，et al. Surveillance，phagocytosis，and inflammation：how never-resting microglia influence adult hippocampal neurogenesis ［J］. Neural Plast，2014,2014:610343.

［7］ Arnò B，Grassivaro F，Rossi C，et al. Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex ［J］. Nat Commun，2014，5:5611.

［8］ Ueno M，Fujita Y，Tanaka T，et al. Layer Ⅴ cortical neurons require microglial support for survival during postnatal development ［J］. Nat Neurosci，2013，16(5)：543-551.

［9］ Shigemoto-Mogami Y，Hoshikawa K，Goldman JE，et al. Microglia enhance neurogenesis and oligodendrogenesis in the early postnatal subventricular zone ［J］. J Neurosci，2014, 34(6)：2231-2243.

［10］ Paolicelli RC，Bolasco G，Pagani F，et al. Synaptic pruning by microglia is necessary for normal brain development ［J］. Science，2011，333(6048)：1456-1458.

［11］ Schafer DP，Lehrman EK，Kautzman AG，et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner ［J］. Neuron，2012，74(4)：691-705.

［12］ Bialas AR，Stevens B. TGF-beta signaling regulates neuronal C1q expression and developmental synaptic refinement ［J］. Nat Neurosci，2013，16(12)：1773-1782.

［13］ Parkhurst CN，Yang G，Ninan Ⅰ，et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor ［J］. Cell，2013，155(7)：1596-1609.

［14］ Elmore MR，Najafi AR，Koike MA，et al. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability，unmasking a microglia progenitor cell in the adult brain ［J］. Neuron，2014，82(2)：380-397.

［15］ Gautier EL，Shay T，Miller J，et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages ［J］. Nat Immunol，2012，13(11)：1118-1128.

［16］ Hoshiko M，Arnoux Ⅰ，Avignone E，et al. Deficiency of the microglial receptor CX3CR1 impairs postnatal functional development of thalamocortical synapses in the barrel cortex ［J］. Neurosci，2012，32(43)：15106-15111.

［17］ Rogers JT，Morganti JM，Bachstetter AD，et al. CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity ［J］. J Neurosci，2011，31(45)：16241-16250.

［18］ Wake H，Moorhouse AJ，Jinno S，et al. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals ［J］. J Neurosci，2009，29(13)：3974-3980.

［19］ Zhu ChG，Li ZhL. Cytokine and immune-neuro-endocrine regulation network ［J］. Acta Anatomica Sinica，1996,27(4)：339-344. (in Chinese)

朱长庚，李正莉. 细胞因子与免疫神经内分泌调节网络［J］. 解剖学报，1996,27 (4)：339-344.

［20］ Schneider H，Pitossi F，Balschun D，et al. A neuromodulatory role of interleukin-1b in the hippocampus ［J］. Proc Natl Acad Sci，1998，95(13)：7778-7783.

［21］ Goshen Ⅰ，Kreisel T，Ounallah-Saad H，et al. A dual role for interleukin-1 in hippocampal-dependent memory processes ［J］. Psychoneuroendocrinology，2007，32(8-10)：1106-1115.

［22］ Viviani B，Bartesaghi S，Gardoni F，et al. Interleukin1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases ［J］. J Neurosci，2003，23(25)：8692-8700.

［23］ Zunszain PA，Anacker C，Cattaneo A，et al. Interleukin-1beta：a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis ［J］. Neuropsychopharmacology，2012，37(4)：939-949.

［24］ Zhang K，Xu H，Cao L，et al. Interleukin-1beta inhibits the differentiation of hippocampal neural precursor cells into serotonergic neurons ［J］. Brain Res，2013，1490：193-201.

［25］ Song C，Phillips AG，Leonard B. Interleukin 1 beta enhances conditioned fear memory in rats：possible involvement of glucocorticoids ［J］. Eur J Neurosci，2003，18(7)：1739-1743.

［26］ Le HL，Luo GQ. Research progress of early inflammatory factors TNF-a，IL-1 and IL-6 after trauma ［J］. Modern Diagnosis & Treatment，2014，25(4)，763-765. (in Chinese)

乐海浪，罗国强. 创伤后早期炎症因子 TNF-a、IL-1、IL-6 的研究进展［J］. 现代诊断与治疗，2014，25(4)，763-765.

［27］ Braida D，Sacerdote P，Panerai AE，et al. Cognitive function in young and adult IL (interleukin)-6 deficient mice ［J］. Behav Brain Res，2004，153(2)：423-429.

［28］ Williamson LL， Bilbo SD. Chemokines and the hippocampus：a new perspective on hippocampal plasticity and vulnerability ［J］. Brain Behav Immun，2013,30:186-194.

［29］ Balschun D，Wetzel W，Del Rey A，et al. Interleukin-6：a cytokine to forget ［J］. FASEB，2004，18(14)：1788-1790.

［30］ Jankowsky JL，Derrick BE，Patterson PH. Cytokine responses to LTP induction in the rat hippocampus：a comparison of in vitro and in vivo techniques ［J］. Learn Mem，2000，7(6)：400-412.

［31］ He Y，Hsuchou H，Wu X，et al. Interleukin-15 receptor is essential to facilitate GABA transmission and hippocampal-dependent memory ［J］. J Neurosci，2010，30(13)：4725-4734.

［32］ Takei Y，Laskey R. Interpreting crosstalk between TNF-alpha and NGF：potential implications for disease ［J］. Trends Mol Med，2008，14(9)：381-388.

［33］ Belarbi K，Jopson T，Tweedie D，et al. TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation ［J］. Neuroinflammation，2012，25(9)：23.

［34］ Butler MP，O’Connor JJ，Moynagh PN. Dissection of tumor-necrosis factor-αinhibition of long-term potentiation (LTP) reveals a p38 mitogen-activated protein kinase-dependent mechanism which maps to early-but not late-phase LTP ［J］. Neuroscience，2004，124(2)：319-326.

［35］ Paredes D，Acosta S，Gemma C，et al. Role of TNFα induced inflammation in delay eye blink conditioning in young and aged rats ［J］. Aging and Disease，2010，1(3)：191-198.

［36］ Baune BT，Wiede F，Braun A，et al. Cognitive dysfunction in mice deficient for TNF- and its receptors ［J］. Am J Med Genet B Neuropsychiatr Genet，2008，147B(7)：1056-1064.

［37］ Fontaine Ⅴ，Mohand-Said S，Hanoteau N，et al. Neurodegenerative and neuroprotective effects of tumor Necrosis factor (TNF) in retinal ischemia：opposite roles of TNF receptor 1 and TNF receptor 2 ［J］. J Neurosci，2002，22(7)：RC216.

［38］ Iosif RE，Ekdahl CT，Ahlenius H，et al. Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis ［J］. J Neurosci，2006，26(38)：9703-9712.

［39］ Naude PJ，Dobos N，van der Meer D，et al. Analysis of cognition，motor performance and anxiety in young and aged tumor necrosis factor alpha receptor 1 and 2 deficient mice ［J］. Behav Brain Res，2014，258：43-51.

［40］ Stellwagen D，Malenka RC. Synaptic scaling mediated by glial TNF-a ［J］. Nature，2006，440(7087)：1054-1059.

［41］ Scherbel U，Raghupathi R，Nakamura M，et al. Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury ［J］. Proc Natl Acad Sci，1999，96(15)：8721-8726.

［42］ Crews FT，Walter TJ，Coleman LG Jr，et al. Toll-like receptor signaling and stages of addiction ［J］. Psychopharmacology，2017，234(9-10)：1483-1498.

［43］ Barak B，Feldman N，Okun E. Toll-like receptors as developmental tools that regulate neurogenesis during development：an update ［J］. Front Neurosci，2014，8：272.

［44］ Okun E，Griffioen KJ，Son TG，et al. TLR2 activation inhibits embryonic neural progenitor cell proliferation ［J］. J Neurochem，2010，114(2)，462-474.

［45］ Rolls A，Shechter R，London A，et al. Toll-like receptors modulate adult hippocampal neurogenesis ［J］. Nat Cell Biol，2007，9(9)：1081-1088.

［46］ Okun E，Griffioen K，Barak B，et al. Toll-like receptor 3 inhibits memory retention and constrains adult hippocampal neurogenesis ［J］. Proc Natl Acad Sci，2010，107(35)：15625-15630.

［47］ Lin CW，Liu HY，Chen CY，et al. Neuronally-expressed Sarm1 regulates expression of inflammatory and antiviral cytokines in brains ［J］. Innate Immun，2014，20(2)：161-172.

［48］ Ziv Y，Ron N，Butovsky O，et al. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood ［J］. Nat Neurosci，2006，9(2)：268-275.

［49］ Huang S，Tao X，Yuan S，et al. Discovery of an active RAG transposon illuminates the origins of Ⅴ(D)J recombination ［J］. Cell，2016，166 (1)：102-114.

［50］ Chun JJ，Schatz DG，Oettinger MA，et al. The recombination activating gene-1 (RAG-1) transcript is present in the murine central nervous system ［J］. Cell，1991，64(1)：189-200.

［51］ McGowan PO，Hope TA，Meck WH，et al. Impaired social recognition memory in recombination activating gene 1-deficient mice ［J］. Brain Res，2011，1383：187-195.

［52］ Derecki NC，Cardani AN，Yang CH，et al. Regulation of learning and memory by meningeal immunity：a key role for IL-4 ［J］. Exp Med，2010，207(5)：1067-1080.

［53］ Baruch K，Schwartz M. CNS-specific T cells shape brain function via the choroid plexus ［J］. Brain Behav Immun，2013，34：11-16.

［54］ Nautiyal KM，Dailey CA，Jahn JL，et al. Serotonin of mast cell origin contributes to hippocampal function ［J］. Eur J Neurosci，2012，36 (3)：2347-2359.

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