内源性大麻素系统对孤独症谱系障碍异常神经炎症反应调控作用的研究进展

谢姝, 刘瑜, 李德欣, 李玲, 邹明扬, 孙彩虹

中国儿童保健杂志 ›› 2022, Vol. 30 ›› Issue (4) : 392-395.

PDF(432 KB)
PDF(432 KB)
中国儿童保健杂志 ›› 2022, Vol. 30 ›› Issue (4) : 392-395. DOI: 10.11852/zgetbjzz2020-1839
综述

内源性大麻素系统对孤独症谱系障碍异常神经炎症反应调控作用的研究进展

  • 谢姝1, 刘瑜1, 李德欣2, 李玲1, 邹明扬1, 孙彩虹1
作者信息 +

Research progress in the regulation of endocannabinoid system on abnormal neuroinflammation in autism spectrum disorder

  • XIE Shu*, LIU Yu, LI De-xin, LI Ling, ZOU Ming-yang, SUN Cai-hong
Author information +
文章历史 +

摘要

孤独症谱系障碍(ASD)是一种严重的神经发育障碍性疾病。近年来,世界各地ASD的患病率均呈上升趋势。目前,越来越多的证据表明,神经炎症反应可能是ASD的病因之一,包括炎性细胞因子异常表达和小胶质细胞异常激活等。内源性大麻素(eCB)系统是中枢神经系统调节的重要调节系统,可调控神经炎症反应,维持机体的免疫平衡。有研究证实,ASD体内存在eCB信号低表达,并且升高eCB信号可以纠正ASD的异常神经炎症反应,从而改善ASD样症状,因此,通过调节eCB系统抑制神经炎症反应可作为治疗ASD的新靶点。综上,本文对eCB系统-神经炎症-ASD三者之间的关系及调控作用进行简要概述。

Abstract

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorders with an increasing prevalence all over the world.Emerging evidence has implicated that neuroinflammation is one of the causes of ASD, including abnormal expression of inflammatory cytokines and abnormal activation of microglia.The endocannabinoid (eCB) system plays a key role in the regulation of the central nervous system, regulating the neuroinflammation and maintaining the immune balance.It has been confirmed that there is decreasing eCB signaling in ASD, and increasing eCB signaling can reduce the abnormal neuroinflammation of ASD and improve ASD symptoms.Therefore, inhibiting neuroinflammation by regulating the eCB system could be a new therapeutic target for ASD.This review combs the relationship and effect among the eCB system, neuroinflammation and ASD.

关键词

孤独症谱系障碍 / 神经炎症 / 细胞因子 / 小胶质细胞 / 内源性大麻素系统

Key words

autism spectrum disorder / neuroinflammation / cytokines / microglia / endocannabinoid system

引用本文

导出引用
谢姝, 刘瑜, 李德欣, 李玲, 邹明扬, 孙彩虹. 内源性大麻素系统对孤独症谱系障碍异常神经炎症反应调控作用的研究进展[J]. 中国儿童保健杂志. 2022, 30(4): 392-395 https://doi.org/10.11852/zgetbjzz2020-1839
XIE Shu, LIU Yu, LI De-xin, LI Ling, ZOU Ming-yang, SUN Cai-hong. Research progress in the regulation of endocannabinoid system on abnormal neuroinflammation in autism spectrum disorder[J]. Chinese Journal of Child Health Care. 2022, 30(4): 392-395 https://doi.org/10.11852/zgetbjzz2020-1839
中图分类号: R741   

参考文献

[1] Francesmonneris A,Pincus H,First M.Diagnostic and statistical manual of mental disorders:DSM-V[M].Washington DC:American Psychiatric Association, 2013.
[2] Maenner MJ,Shaw KA,Bakian AV,et al.Prevalence and characteristics of autism spectrum disorder among children aged 8 years-autism and developmental disabilities monitoring network, 11 sites, United States, 2018[J].MMWR Surveill Summ,2021,70(11):1-16.
[3] Saghazadeh A,Ataeinia B,Keynejad K,et al.A meta-analysis of pro-inflammatory cytokines in autism spectrum disorders:Effects of age, gender, and latitude[J].J Psychiatr Res,2019,115:90-102.
[4] Saghazadeh A,Ataeinia B,Keynejad K,et al.Anti-inflammatory cytokines in autism spectrum disorders:A systematic review and meta-analysis[J].Cytokine,2019,123:154740.
[5] Siniscalco D,Sapone A,Giordano C,et al.The expression of caspases is enhanced in peripheral blood mononuclear cells of autism spectrum disorder patients[J].J Autism Dev Disord,2012,42(7):1403-1410.
[6] Bennabi M,Tarantino N,Gaman A,et al.Persistence of dysfunctional natural killer cells in adults with high-functioning autism spectrum disorders:stigma/consequence of unresolved early infectious events?[J].Mol Autism,2019,10:22.
[7] Enstrom AE,Lit L,Onore CE,et al.Altered gene expression and function of peripheral blood natural killer cells in children with autism[J].Brain Behav Immun,2009,23(1):124-133.
[8] Rose DR,Careaga M,van de Water J,et al.Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation[J].Brain Behav Immun,2017,63:60-70.
[9] Custódio CS,Mello BSF,Filho A,et al.Neonatal immune challenge with lipopolysaccharide triggers long-lasting sex-and age-related behavioral and immune/neurotrophic alterations in mice:relevance to autism spectrum disorders[J].Mol Neurobiol,2018,55(5):3775-3788.
[10] Vargas DL,Nasclmbene C,Krishnan C,et al.Neuroglial activation and neuroinflammation in the brain of patients with autism[J].Ann Neurol,2005,57(1):67-81.
[11] Careaga M,Ashwood P.Autism spectrum disorders:from immunity to behavior[J].Methods Mol Biol,2012,934:219-240.
[12] Tsilioni I,Patel AB,Pantazopoulos H,et al.IL-37 is increased in brains of children with autism spectrum disorder and inhibits human microglia stimulated by neurotensin[J].Proc Natl Acad Sci U S A,2019,116(43):21659-21665.
[13] Yang I, Hang SJ, Kaar G,et al.The role of microglia in central nervous system immunity and glioma immunology[J].J Clin Neurosci,2010,17(1):6-10.
[14] Janda E,Boi L,Carta AR.Microglial phagocytosis and its regulation:a therapeutic target in parkinson's disease?[J].Front Mol Neurosci,2018,11:144.
[15] Tsilioni I,Theoharides TC.Extracellular vesicles are increased in the serum of children with autism spectrum disorder, contain mitochondrial DNA, and stimulate human microglia to secrete IL-1β[J].J Neuroinflammation,2018,15(1):239.
[16] Morgan JT,Chana G,Pardo CA,et al.Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism[J].Biol Psychiatry,2010,68(4):368-376.
[17] Suzuki K,Sugihara G,Ouchi Y,et al.Microglial activation in young adults with autism spectrum disorder[J].JAMA Psychiatry,2013,70(1):49-58.
[18] Eldin J,Tracy LB,Christopher LH,et al.Alterations in the vaginal microbiome by maternal stress are associated with metabolic reprogramming of the offspring gut and brain[J].Endocrinology,2015,156(9):3265-3276.
[19] Hind WH, Tufarelli G, Neophytou M, et al.Endocannabinoids modulate human blood-brain barrier permeability in vitro[J].Brit J Pharmacol,2015,172(12):3015-3027.
[20] Pál P,Sándor B,George K.The endocannabinoid system as an emerging target of pharmacotherapy[J].Pharmacol Rev,2006,58(3):389-462.
[21] Kwan CKA,Hassendrini P,Geoffrey W,et al.The Interplay between the endocannabinoid system, epilepsy and cannabinoids[J].Int J Mol Sci,2019,20(23):6079.
[22] Xu JY,Chen C. Endocannabinoids in synaptic plasticity and neuroprotection[J].Neuroscientist,2015,21(2):152-168.
[23] Wolf SA, Ullrich D.Endocannabinoids and the brain immune system:new neurones at the horizon?[J].J Neuroendocrinol,2008,20 (Suppl 1):15-19.
[24] Mecha M,Yanguas-Casás N,Feliú A,et al.The endocannabinoid 2-AG enhances spontaneous remyelination by targeting microglia[J].Brain Behav Immun,2019,77:110-126.
[25] Frida L,Stefania P,Leyre M,et al.Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide[J].Eur J Neurosci,2008,28(4):633-641.
[26] Fernández-Suárez D,Celorrio M,Riezuh Boj JI, et al.Monoacylglycerol lipase inhibitor JZL184 is neuroprotective and alters glial cell phenotype in the chronic MPTP mouse model[J].Neurobiol Aging,2014,35(11):2603-2616.
[27] Kelly R,Joers V,Tansey MG,et al.Microglial phenotypes and their relationship to the cannabinoid system:therapeutic implications for parkinson's disease[J].Molecules,2020,25(3):453.
[28] Talarico G,Trebbastoni A,Bruno G,et al.Modulation of the cannabinoid system:a new perspective for the treatment of the alzheimer's disease[J].Curr Neuropharmacol,2019,17(2):176-183.
[29] Navarro G,Borroto-Escuela D,Angelats E,et al.Receptor-heteromer mediated regulation of endocannabinoid signaling in activated microglia.Role of CB(1) and CB(2) receptors and relevance for Alzheimer's disease and levodopa-induced dyskinesia[J].Brain Behav Immun,2018,67:139-151.
[30] Kempuraj D,Thangavel R,Natteru PA,et al.Neuroinflammation induces neurodegeneration[J].J Neurol Neurosurg Spine,2016,1(1):1003.
[31] 李德欣.ASD 儿童 eCB 系统表达水平及其与表型特征的关联研究[D].哈尔滨:哈尔滨医科大学,2020.
[32] Servadio M,Melancia F,Manduca A,et al.Targeting anandamide metabolism rescues core and associated autistic-like symptoms in rats prenatally exposed to valproic acid[J].Transl Psychiatry,2016,6(9):e902.
[33] Kerr DM,Downey L,Conboy M,et al.Alterations in the endocannabinoid system in the rat valproic acid model of autism[J].Behav Brain Res,2013,249:124-132.
[34] Aran A,Eylon M,Harel M,et al.Lower circulating endocannabinoid levels in children with autism spectrum disorder[J].Mol Autism,2019,10:2.
[35] Habib SS,Al-Regaiey K,Bashir S,et al.Role of Endocannabinoids on neuroinflammation in autism spectrum disorder prevention[J].J Clin Diagn Res,2017,11(6):ce01-ce03.
[36] Antonucci N,Cirillo A,Siniscalco D.Beneficial effects of palmitoylethanolamide on expressive language, cognition, and behaviors in autism:a report of two cases[J].Case Rep Psychiatry,2015,2015:325061.
[37] Bertolino B,Crupi R,Impellizzeri D,et al.Beneficial effects of co-ultramicronized palmitoylethanolamide/luteolin in a mouse model of autism and in a case report of autism[J].CNS Neurosci Ther,2017,23(1):87-98.
[38] Wei D,Dinh D,Lee D,et al.Enhancement of anandamide-mediated endocannabinoid signaling corrects autism-related social impairment[J].Cannabis Cannabinoid Res,2016,1(1):81-89.
[39] Erica Z,Marina G,Marie W-R,et al.Cannabidivarin treatment ameliorates autism-like behaviors and restores hippocampal endocannabinoid system and glia alterations induced by prenatal valproic acid exposure in rats[J].Front Cell Neurosci,2019,13:367.

基金

国家自然科学青年基金(81903348)

PDF(432 KB)

Accesses

Citation

Detail

段落导航
相关文章

/