Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders

Abraham, 2010, Mast cell-orchestrated immunity to pathogens, Nat. Rev. Immunol., 10, 440, 10.1038/nri2782 Abuhatzira, 2007, MeCP2 deficiency in the brain decreases BDNF levels by REST/CoREST-mediated repression and increases TRKB production, Epigenetics, 2, 214, 10.4161/epi.2.4.5212 Akin, 2010, Mast cell activation syndrome: proposed diagnostic criteria, J. Allergy Clin. Immunol., 126, 1099, 10.1016/j.jaci.2010.08.035 Aldinger, 2011, SnapShot: genetics of autism, Neuron, 72, 418, 10.1016/j.neuron.2011.10.007 Angelidou, 2010, Neurotensin is increased in serum of young children with autistic disorder, J. Neuroinflammation, 7, 48, 10.1186/1742-2094-7-48 Angelidou, 2011, Brief report: “allergic symptoms” in children with autism spectrum disorders. More than meets the eye?, J. Autism Dev. Disord., 41, 1579, 10.1007/s10803-010-1171-z Angelidou, 2012, Perinatal stress, brain inflammation and risk of autism—review and proposal, BMC Pediatr., 12, 89, 10.1186/1471-2431-12-89 Antonelli, 2004, Neurotensin enhances endogenous extracellular glutamate levels in primary cultures of rat cortical neurons: involvement of neurotensin receptor in NMDA induced excitotoxicity, Cereb. Cortex, 14, 466, 10.1093/cercor/bhh008 Armstrong, 2005, Neuropathology of Rett syndrome, J. Child Neurol., 20, 747, 10.1177/08830738050200082401 Asadi, 2012, Corticotropin-releasing hormone and extracellular mitochondria augment IgE-stimulated human mast-cell vascular endothelial growth factor release, which is inhibited by luteolin, J. Neuroinflammation, 9, 85, 10.1186/1742-2094-9-85 Ashwood, 2004, Is autism an autoimmune disease?, Autoimmun. Rev., 3, 557, 10.1016/j.autrev.2004.07.036 Autry, 2012, Brain-derived neurotrophic factor and neuropsychiatric disorders, Pharmacol. Rev., 64, 238, 10.1124/pr.111.005108 Banerjee, 2012, Rett syndrome: genes, synapses, circuits, and therapeutics, Front. Psychiatry, 3, 34, 10.3389/fpsyt.2012.00034 Bauman, 2010, Medical comorbidities in autism: challenges to diagnosis and treatment, Neurotherapeutics, 7, 320, 10.1016/j.nurt.2010.06.001 Beversdorf, 2005, Timing of prenatal stressors and autism, J. Autism Dev. Disord., 35, 471, 10.1007/s10803-005-5037-8 Blackman, 2012, A critical and cell-autonomous role for MeCP2 in synaptic scaling up, J. Neurosci., 32, 13529, 10.1523/JNEUROSCI.3077-12.2012 Braunschweig, 2012, Maternal autoantibodies in autism, Arch. Neurol., 69, 693, 10.1001/archneurol.2011.2506 Brimberg, 2013, Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder, 18, 1171 Cao, 2005, Human mast cells express corticotropin-releasing hormone (CRH) receptors and CRH leads to selective secretion of vascular endothelial growth factor, J. Immunol., 174, 7665, 10.4049/jimmunol.174.12.7665 Careaga, 2013, Increased anti-phospholipid antibodies in autism spectrum disorders, Mediat. Inflamm., 2013, 935608, 10.1155/2013/935608 Castro, 2013, Mechanisms and therapeutic challenges in autism spectrum disorders: insights from Rett syndrome, Curr. Opin. Neurol., 26, 154, 10.1097/WCO.0b013e32835f19a7 Chahrour, 2008, MeCP2, a key contributor to neurological disease, activates and represses transcription, Science, 320, 1224, 10.1126/science.1153252 Correia, 2010, Increased BDNF levels and NTRK2 gene association suggest a disruption of BDNF/TrkB signaling in autism, Genes Brain Behav., 9, 841, 10.1111/j.1601-183X.2010.00627.x Corriden, 2010, Basal release of ATP: an autocrine–paracrine mechanism for cell regulation, Sci. Signal., 3, re1, 10.1126/scisignal.3104re1 Dahlgren, 2006, Interleukin-6 in the maternal circulation reaches the rat fetus in mid-gestation, Pediatr. Res., 60, 147, 10.1203/01.pdr.0000230026.74139.18 Degano, 2009, MeCP2 deficiency disrupts axonal guidance, fasciculation, and targeting by altering Semaphorin 3F function, Mol. Cell. Neurosci., 42, 243, 10.1016/j.mcn.2009.07.009 Delgado, 2006, Expression profiling of clonal lymphocyte cell cultures from Rett syndrome patients, BMC Med. Genet., 7, 61, 10.1186/1471-2350-7-61 Derecki, 2010, Rett syndrome and other autism spectrum disorders—brain diseases of immune malfunction?, Mol. Psychiatry, 15, 355, 10.1038/mp.2010.21 Derecki, 2012, Wild-type microglia arrest pathology in a mouse model of Rett syndrome, Nature, 484, 105, 10.1038/nature10907 Derecki, 2013, The role of microglia in brain maintenance: implications for Rett syndrome, Trends Immunol., 34, 144, 10.1016/j.it.2012.10.002 Donelan, 2006, Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process, Proc. Natl. Acad. Sci. U. S. A., 103, 7759, 10.1073/pnas.0602210103 Esposito, 2002, Corticotropin-releasing hormone (CRH) and brain mast cells regulate blood–brain-barrier permeability induced by acute stress, J. Pharmacol. Exp. Ther., 303, 1061, 10.1124/jpet.102.038497 Fatokun, 2013, Identification through high-throughput screening of 4′-methoxyflavone and 3′,4′-dimethoxyflavone as novel neuroprotective inhibitors of parthanatos, Br. J. Pharmacol., 169, 1263, 10.1111/bph.12201 Feng, 2009, The role of DNA methylation in the central nervous system and neuropsychiatric disorders, Int. Rev. Neurobiol., 89, 67, 10.1016/S0074-7742(09)89004-1 Fombonne, 2009, Epidemiology of pervasive developmental disorders, Pediatr. Res., 65, 591, 10.1203/PDR.0b013e31819e7203 Galli, 2008, The development of allergic inflammation, Nature, 454, 445, 10.1038/nature07204 Gesundheit, 2013, Immunological and autoimmune considerations of autism spectrum disorders, J. Autoimmun., 44, 1, 10.1016/j.jaut.2013.05.005 Ghanizadeh, 2010, Targeting neurotensin as a potential novel approach for the treatment of autism, J. Neuroinflammation, 7, 58, 10.1186/1742-2094-7-58 Gillott, 2007, Levels of anxiety and sources of stress in adults with autism, J. Intellect. Disabil., 11, 359, 10.1177/1744629507083585 Guy, 2007, Reversal of neurological defects in a mouse model of Rett syndrome, Science, 315, 1143, 10.1126/science.1138389 Hallmayer, 2011, Genetic heritability and shared environmental factors among twin pairs with autism, Arch. Gen. Psychiatry, 68, 1095, 10.1001/archgenpsychiatry.2011.76 Harwood, 2007, A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties, Food Chem. Toxicol., 45, 2179, 10.1016/j.fct.2007.05.015 Herbert, 2010, Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders, Curr. Opin. Neurol., 23, 103, 10.1097/WCO.0b013e328336a01f Hsiao, 2012, Modeling an autism risk factor in mice leads to permanent immune dysregulation, Proc. Natl. Acad. Sci. U. S. A., 109, 12776, 10.1073/pnas.1202556109 Jager, 2011, Flavonoids and the CNS, Molecules, 16, 1471, 10.3390/molecules16021471 Jang, 2008, Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1, Proc. Natl. Acad. Sci. U. S. A., 105, 7534, 10.1073/pnas.0802865105 Jang, 2010, A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone, Proc. Natl. Acad. Sci. U. S. A., 107, 2687, 10.1073/pnas.0913572107 Johnson, 2012, 7,8-Dihydroxyflavone exhibits therapeutic efficacy in a mouse model of Rett syndrome, J. Appl. Physiol., 112, 704, 10.1152/japplphysiol.01361.2011 Jones, 2012, Target-based selection of flavonoids for neurodegenerative disorders, Trends Pharmacol. Sci., 33, 602, 10.1016/j.tips.2012.08.002 Jyonouchi, 2010, Autism spectrum disorders and allergy: observation from a pediatric allergy/immunology clinic, Expert. Rev. Clin. Immunol., 6, 397, 10.1586/eci.10.18 Kandere-Grzybowska, 2003, IL-1 induces vesicular secretion of IL-6 without degranulation from human mast cells, J. Immunol., 171, 4830, 10.4049/jimmunol.171.9.4830 Karagkouni, 2013, Effect of stress on brain inflammation and multiple sclerosis, Autoimmun. Rev., 12, 947, 10.1016/j.autrev.2013.02.006 Katz, 2014, Brain-derived neurotrophic factor and Rett syndrome, Handb. Exp. Pharmacol., 220, 481, 10.1007/978-3-642-45106-5_18 Kempuraj, 2008, Luteolin inhibits myelin basic protein-induced human mast cell activation and mast cell dependent stimulation of Jurkat T cells, Br. J. Pharmacol., 155, 1076, 10.1038/bjp.2008.356 Kimata, 2000, Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells, Clin. Exp. Allergy, 30, 501, 10.1046/j.1365-2222.2000.00768.x Klushnik, 2001, Brain-directed autoantibodies levels in the serum of Rett syndrome patients, Brain Dev., 23, S113, 10.1016/S0387-7604(01)00353-9 Kogan, 2009, Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007, Pediatrics, 5, 1395, 10.1542/peds.2009-1522 Ku, 2013, A new paradigm emerges from the study of de novo mutations in the context of neurodevelopmental disease, Mol. Psychiatry, 18, 141, 10.1038/mp.2012.58 Lauritzen, 2010, Mitochondrial DNA toxicity in forebrain neurons causes apoptosis, neurodegeneration, and impaired behavior, Mol. Cell. Biol., 30, 1357, 10.1128/MCB.01149-09 Li, 2014, BDNF deregulation in Rett syndrome, Neuropharmacology, 76 Pt C, 737, 10.1016/j.neuropharm.2013.03.024 Li, 2009, Elevated immune response in the brain of autistic patients, J. Neuroimmunol., 207, 111, 10.1016/j.jneuroim.2008.12.002 Lilja, 2013, Novel alterations in the epigenetic signature of MeCP2-targeted promoters in lymphocytes of Rett syndrome patients, Epigenetics, 8, 246, 10.4161/epi.23752 Maezawa, 2009, Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions, J. Neurosci., 29, 5051, 10.1523/JNEUROSCI.0324-09.2009 Maezawa, 2011, Does microglial dysfunction play a role in autism and Rett syndrome?, Neuron Glia Biol., 7, 85, 10.1017/S1740925X1200004X Matijevic, 2009, Rett syndrome: from the gene to the disease, Eur. Neurol., 61, 3, 10.1159/000165342 Matsuishi, 2011, Rett syndrome: the state of clinical and basic research, and future perspectives, Brain Dev., 33, 627, 10.1016/j.braindev.2010.12.007 Mazur-Kolecka, 2014, Autoantibodies against neuronal progenitors in sera from children with autism, Brain Dev., 36, 322, 10.1016/j.braindev.2013.04.015 Middleton, 2000, The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer, Pharmacol. Rev., 52, 673 Morgan, 2012, Abnormal microglial–neuronal spatial organization in the dorsolateral prefrontal cortex in autism, Brain Res., 1456, 72, 10.1016/j.brainres.2012.03.036 Mostafa, 2013, The possible relationship between allergic manifestations and elevated serum levels of brain specific auto-antibodies in autistic children, J. Neuroimmunol., 261, 77, 10.1016/j.jneuroim.2013.04.003 Moura, 2014, Neuropsychological features of adult mastocytosis, Immunol. Allergy Clin. N. Am., 34, 407, 10.1016/j.iac.2014.02.001 Mustain, 2011, The role of neurotensin in physiologic and pathologic processes, Curr. Opin. Endocrinol. Diabetes Obes., 18, 75, 10.1097/MED.0b013e3283419052 Na, 2013, The impact of MeCP2 loss- or gain-of-function on synaptic plasticity, Neuropsychopharmacology, 38, 212, 10.1038/npp.2012.116 Nakae, 2007, Mast cell-derived TNF can promote Th17 cell-dependent neutrophil recruitment in ovalbumin-challenged OTII mice, Blood, 109, 3640, 10.1182/blood-2006-09-046128 Naviaux, 2013, Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model, PLoS One, 8, e57380, 10.1371/journal.pone.0057380 Naviaux, 2014, Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy, Transl. Psychiatry, 4, e400, 10.1038/tp.2014.33 Neul, 2010, Rett syndrome: revised diagnostic criteria and nomenclature, Ann. Neurol., 68, 944, 10.1002/ana.22124 Nguyen, 2012, MeCP2 is critical for maintaining mature neuronal networks and global brain anatomy during late stages of postnatal brain development and in the mature adult brain, J. Neurosci., 32, 10021, 10.1523/JNEUROSCI.1316-12.2012 Nishimura, 2007, Genetic analyses of the brain-derived neurotrophic factor (BDNF) gene in autism, Biochem. Biophys. Res. Commun., 356, 200, 10.1016/j.bbrc.2007.02.135 Parker-Athill, 2009, Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism, J. Neuroimmunol., 217, 20, 10.1016/j.jneuroim.2009.08.012 Petra, 2014, Spectrum of mast cell activation disorders, Expert. Rev. Clin. Immunol., 10, 729, 10.1586/1744666X.2014.906302 Piras, 2014, Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with autism spectrum disorder, Brain Behav. Immun., 38, 91, 10.1016/j.bbi.2013.12.020 Qiu, 2012, The Rett syndrome protein MeCP2 regulates synaptic scaling, J. Neurosci., 32, 989, 10.1523/JNEUROSCI.0175-11.2012 Rangasamy, 2013, Epigenetics, autism spectrum, and neurodevelopmental disorders, Neurotherapeutics, 10, 742, 10.1007/s13311-013-0227-0 Ricci, 2013, Altered cytokine and BDNF levels in autism spectrum disorder, Neurotox. Res., 24, 491, 10.1007/s12640-013-9393-4 Rodriguez, 2011, Evidence of microglial activation in autism and its possible role in brain underconnectivity, Neuron Glia Biol., 7, 205, 10.1017/S1740925X12000142 Ronald, 2010, Prenatal maternal stress associated with ADHD and autistic traits in early childhood, Front. Psychol., 1, 223 Rossi, 2011, Detection of plasma autoantibodies to brain tissue in young children with and without autism spectrum disorders, Brain Behav. Immun., 25, 1123, 10.1016/j.bbi.2011.02.011 Rossignol, 2012, Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis, Mol. Psychiatry, 17, 290, 10.1038/mp.2010.136 Rossignol, 2014, Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism, Front. Physiol., 5, 10.3389/fphys.2014.00150 Rottem, 2005, Mast cells and autoimmunity, Autoimmun. Rev., 4, 21, 10.1016/j.autrev.2004.05.001 Sadakata, 2012, Reduced axonal localization of a Caps2 splice variant impairs axonal release of BDNF and causes autistic-like behavior in mice, Proc. Natl. Acad. Sci. U. S. A., 109, 21104, 10.1073/pnas.1210055109 Samaco, 2009, Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities, Proc. Natl. Acad. Sci. U. S. A., 106, 21966, 10.1073/pnas.0912257106 Schaevitz, 2010, Cognitive and social functions and growth factors in a mouse model of Rett syndrome, Physiol. Behav., 100, 255, 10.1016/j.physbeh.2009.12.025 Singh, 2014, Sulforaphane treatment of autism spectrum disorder (ASD), Proc. Natl. Acad. Sci. U. S. A., 111, 15550, 10.1073/pnas.1416940111 Skaper, 2012, Microglia and mast cells: two tracks on the road to neuroinflammation, FASEB J., 26, 3103, 10.1096/fj.11-197194 Smith, 2007, Maternal immune activation alters fetal brain development through interleukin-6, J. Neurosci., 27, 10695, 10.1523/JNEUROSCI.2178-07.2007 Smith, 2011, Neurologic symptoms and diagnosis in adults with mast cell disease, Clin. Neurol. Neurosurg., 113, 570, 10.1016/j.clineuro.2011.05.002 Suurmond, 2011, Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium, Arthritis Res. Ther., 13, R150, 10.1186/ar3466 Taliou, 2013, An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders, Clin. Ther., 35, 592, 10.1016/j.clinthera.2013.04.006 Theoharides, 1990, Mast cells: the immune gate to the brain, Life Sci., 46, 607, 10.1016/0024-3205(90)90129-F Theoharides, 2009, Autism spectrum disorders and mastocytosis, Int. J. Immunopathol. Pharmacol., 22, 859, 10.1177/039463200902200401 Theoharides, 2013, Extracellular mitochondrial components secreted from activated live mast cells act as innate pathogens and contribute to autism pathogenesis, Int. Trends Immun., 1, 5 Theoharides, 2013, Is a subtype of autism “allergy of the brain”?, Clin. Ther., 35, 584, 10.1016/j.clinthera.2013.04.009 Theoharides, 2008, Autism, gut–blood–brain barrier and mast cells, J. Clin. Psychopharmacol., 28, 479, 10.1097/JCP.0b013e3181845f48 Theoharides, 2007, Corticotropin-releasing hormone and the blood–brain-barrier, Front. Biosci., 12, 1615, 10.2741/2174 Theoharides, 2002, Serum interleukin-6 reflects disease severity and osteoporosis in mastocytosis patients, Int. Arch. Allergy Immunol., 128, 344, 10.1159/000063858 Theoharides, 2007, Differential release of mast cell mediators and the pathogenesis of inflammation, Immunol. Rev., 217, 65, 10.1111/j.1600-065X.2007.00519.x Theoharides, 2008, Novel therapeutic targets for autism, Trends Pharmacol. Sci., 29, 375, 10.1016/j.tips.2008.06.002 Theoharides, 2009, Autism: an emerging ‘neuroimmune disorder’ in search of therapy, Expert. Opin. Pharmacother., 10, 2127, 10.1517/14656560903107789 Theoharides, 2010, Mast cells and inflammation, Biochim. Biophys. Acta, 1822, 21, 10.1016/j.bbadis.2010.12.014 Theoharides, 2010, IL-33 augments substance P-induced VEGF secretion from human mast cells and is increased in psoriatic skin, Proc. Natl. Acad. Sci. U. S. A., 107, 4448, 10.1073/pnas.1000803107 Theoharides, 2011, Decreased mitochondrial function and increased brain inflammation in bipolar disorder and other neuropsychiatric diseases, J. Clin. Psychopharmacol., 31, 685, 10.1097/JCP.0b013e318239c190 Theoharides, 2012, Mast cell activation and autism, Biochim. Biophys. Acta, 1822, 34, 10.1016/j.bbadis.2010.12.017 Theoharides, 2012, A case series of a luteolin formulation (NeuroProtek(R)) in children with autism spectrum disorders, Int. J. Immunopathol. Pharmacol., 25, 317, 10.1177/039463201202500201 Theoharides, 2013, The “missing link” in autoimmunity and autism: extracellular mitochondrial components secreted from activated live mast cells, Autoimmun. Rev., 12, 1136, 10.1016/j.autrev.2013.06.018 Theoharides, 2014, High serum corticotropin-releasing hormone (CRH) and bone marrow mast cell CRH receptor expression in a mastocytosis patient, J. Allergy Clin. Immunol., 134, 1197, 10.1016/j.jaci.2014.05.023 Tsai, 2012, Peripheral administration of brain-derived neurotrophic factor to Rett syndrome animal model: a possible approach for the treatment of Rett syndrome, Med. Sci. Monit., 18, HY33, 10.12659/MSM.883251 Tsilioni, 2014, Elevated serum neurotensin and CRH levels in children with autistic spectrum disorders and tail-chasing bull terriers with a phenotype similar to autism, Transl. Psychiatry, 4, e466, 10.1038/tp.2014.106 Urdinguio, 2008, Mecp2-null mice provide new neuronal targets for Rett syndrome, PLoS One, 3, e3669, 10.1371/journal.pone.0003669 varez-Saavedra, 2007, Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis, Hum. Mol. Genet., 16, 2315, 10.1093/hmg/ddm185 Vargas, 2005, Neuroglial activation and neuroinflammation in the brain of patients with autism, Ann. Neurol., 57, 67, 10.1002/ana.20315 Voehringer, 2013, Protective and pathological roles of mast cells and basophils, Nat. Rev. Immunol., 13, 362, 10.1038/nri3427 Volkmar, 2009, Autism and autism spectrum disorders: diagnostic issues for the coming decade, J. Child Psychol. Psychiatry, 50, 108, 10.1111/j.1469-7610.2008.02010.x Walker, 2012, New insights into the role of mast cells in autoimmunity: evidence for a common mechanism of action?, Biochim. Biophys. Acta, 1822, 57, 10.1016/j.bbadis.2011.02.009 Walle, 2007, Methylation of dietary flavones greatly improves their hepatic metabolic stability and intestinal absorption, Mol. Pharm., 4, 826, 10.1021/mp700071d Walsh, 2014, T cells in the central nervous system: messengers of destruction or purveyors of protection?, Immunology, 141, 340, 10.1111/imm.12187 Walsh, 2014, Regulatory T cells in central nervous system injury: a double-edged sword, J. Immunol., 193, 5013, 10.4049/jimmunol.1302401 Webb, 2009, Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus, Arthritis Rheum., 60, 1076, 10.1002/art.24360 Weiss, 2009, A genome-wide linkage and association scan reveals novel loci for autism, Nature, 461, 802, 10.1038/nature08490 Weng, 2014, Luteolin inhibits human keratinocyte activation and decreases NF-kappaB induction that is increased in psoriatic skin, PLoS One, 9, e90739, 10.1371/journal.pone.0090739 Weng, 2014, The novel flavone tetramethoxyluteolin is a potent inhibitor of human mast cells, J. Allergy Clin. Immunol., 10.1016/j.jaci.2014.10.032 Williams, 2012, Genetics: searching for answers, Nature, 491, S4, 10.1038/491S4a Wills, 2009, Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders, Brain Behav. Immun., 23, 64, 10.1016/j.bbi.2008.07.007 Yaghmaie, 2013, Mental health comorbidity in patients with atopic dermatitis, J. Allergy Clin. Immunol., 131, 428, 10.1016/j.jaci.2012.10.041 Zachariah, 2012, Novel MeCP2 isoform-specific antibody reveals the endogenous MeCP2E1 expression in murine brain, primary neurons and astrocytes, PLoS One, 7, e49763, 10.1371/journal.pone.0049763 Zhang, 2010, Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic children, J. Neuroinflammation, 7, 80, 10.1186/1742-2094-7-80 Zhang, 2011, Human mast cell degranulation and preformed TNF secretion require mitochondrial translocation to exocytosis sites: relevance to atopic dermatitis, J. Allergy Clin. Immunol., 127, 1522, 10.1016/j.jaci.2011.02.005 Zhang, 2012, Stimulated human mast cells secrete mitochondrial components that have autocrine and paracrine inflammatory actions, PLoS One, 7, e49767, 10.1371/journal.pone.0049767 Zhang, 2012, Mitochondria distinguish granule-stored from de novo synthesized tumor necrosis factor secretion in human mast cells, Int. Arch. Allergy Immunol., 159, 23, 10.1159/000335178 Zhang, 2012, Mast cell tryptase induces microglia activation via protease-activated receptor 2 signaling, Cell. Physiol. Biochem., 29, 931, 10.1159/000171029 Zimmerman, 2005, Cerebrospinal fluid and serum markers of inflammation in autism, Pediatr. Neurol., 33, 195, 10.1016/j.pediatrneurol.2005.03.014