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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Review Article (Mini-Review)

Inflammation and Mitochondrial Dysfunction in Autism Spectrum Disorder

Author(s): Maria Gevezova, Victoria Sarafian*, George Anderson and Michael Maes

Volume 19 , Issue 5 , 2020

Page: [320 - 333] Pages: 14

DOI: 10.2174/1871527319666200628015039

Price: $65

Abstract

Autism Spectrum Disorders (ASD) is a severe childhood psychiatric condition with an array of cognitive, language and social impairments that can significantly impact family life. ASD is classically characterized by reduced communication skills and social interactions, with limitations imposed by repetitive patterns of behavior, interests, and activities. The pathophysiology of ASD is thought to arise from complex interactions between environmental and genetic factors within the context of individual development. A growing body of research has raised the possibility of identifying the aetiological causes of the disorder. This review highlights the roles of immune-inflammatory pathways, nitro-oxidative stress and mitochondrial dysfunctions in ASD pathogenesis and symptom severity. The role of NK-cells, T helper, T regulatory and B-cells, coupled with increased inflammatory cytokines, lowered levels of immune-regulatory cytokines, and increased autoantibodies and microglial activation is elucidated. It is proposed that alterations in mitochondrial activity and nitrooxidative stress are intimately associated with activated immune-inflammatory pathways. Future research should determine as to whether the mitochondria, immune-inflammatory activity and nitrooxidative stress changes in ASD affect the development of amygdala-frontal cortex interactions. A number of treatment implications may arise, including prevention-orientated prenatal interventions, treatment of pregnant women with vitamin D, and sodium butyrate. Treatments of ASD children and adults with probiotics, sodium butyrate and butyrate-inducing diets, antipurinergic therapy with suramin, melatonin, oxytocin and taurine are also discussed.

Keywords: Autism, inflammation, neuroimmunomodulation, mitochondrial dysfunction, oxidative stress toxicity, Autism Spectrum Disorders (ASD).

Graphical Abstract
[1]
Karst JS, Van Hecke AV. Parent and family impact of autism spectrum disorders: A review and proposed model for intervention evaluation. Clin Child Fam Psychol Rev 2012; 15(3): 247-77.
[http://dx.doi.org/10.1007/s10567-012-0119-6] [PMID: 22869324]
[2]
El Fotoh WMMA, El Naby SAA, Abd El Hady NMS, Nahla M. Autism spectrum disorders: The association with inherited metabolic disorders and some trace elements. A retrospective study. CNS Neurol Disord Drug Targets 2019; 18(5): 413-20.
[http://dx.doi.org/10.2174/1871527318666190430162724 ] [PMID: 31208314]
[3]
Famitafreshi H, Karimian M. Overview of the recent advances in pathophysiology and treatment for autism. CNS Neurol Disord Drug Targets 2018; 17(8): 590-4.
[http://dx.doi.org/10.2174/1871527317666180706141654 ] [PMID: 29984672]
[4]
Emberti GL, Mazzone L, Benvenuto A, et al. Risk and protective environmental factors associated with autism spectrum disorder: Evidence-based principles and recommendations. J Clin Med 2019; 8(2): 217.
[http://dx.doi.org/10.3390/jcm8020217] [PMID: 30744008]
[5]
Miles JH. Autism spectrum disorders- A genetics review. Genet Med 2011; 13(4): 278-94.
[http://dx.doi.org/10.1097/GIM.0b013e3181ff67ba ] [PMID: 21358411]
[6]
Liu H, Talalay P, Fahey JW. Biomarker-guided strategy for treatment of Autism Spectrum Disorder (ASD). CNS Neurol Disord Drug Targets 2016; 15(5): 602-13.
[http://dx.doi.org/10.2174/1871527315666160413120414 ] [PMID: 27071792]
[7]
Arndt TL, Stodgell CJ, Rodier PM. The teratology of autism. Int J Dev Neurosci 2005; 23(2-3): 189-99.
[http://dx.doi.org/10.1016/j.ijdevneu.2004.11.001] [PMID: 15749245]
[8]
Herbert MR. Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol 2010; 23(2): 103-10.
[http://dx.doi.org/10.1097/WCO.0b013e328336a01f ] [PMID: 20087183]
[9]
Frye RE, Rossignol DA. Mitochondrial dysfunction can connect the diverse medical symptoms associated with autism spectrum disorders. Pediatr Res 2011; 69(5 Pt 2): 41R-7R.
[http://dx.doi.org/10.1203/PDR.0b013e318212f16b ] [PMID: 21289536]
[10]
Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: A systematic review and meta-analysis. Mol Psychiatry 2012; 17(3): 290-314.
[http://dx.doi.org/10.1038/mp.2010.136] [PMID: 21263444]
[11]
Rossignol DA, Frye RE. A review of research trends in physiological abnormalities in autism spectrum disorders: Immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol Psychiatry 2012; 17(4): 389-401.
[http://dx.doi.org/10.1038/mp.2011.165] [PMID: 22143005]
[12]
Jyonouchi H, Geng L, Streck DL, Toruner GA. Children with Autism Spectrum Disorders (ASD) who exhibit chronic Gastrointestinal (GI) symptoms and marked fluctuation of behavioral symptoms exhibit distinct innate immune abnormalities and transcriptional profiles of Peripheral Blood (PB) monocytes. J Neuroimmunol 2011; 238(1-2): 73-80.
[http://dx.doi.org/10.1016/j.jneuroim.2011.07.001] [PMID: 21803429]
[13]
Maes M, DeVos N, Wauters A, et al. Inflammatory markers in younger vs elderly normal volunteers and in patients with Alzheimer’s disease. J Psychiatr Res 1999; 33(5): 397-405.
[http://dx.doi.org/10.1016/S0022-3956(99)00016-3 ] [PMID: 10504008]
[14]
Berk M, Williams LJ, Jacka FN, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med 2013; 11: 200.
[http://dx.doi.org/10.1186/1741-7015-11-200] [PMID: 24228900]
[15]
Leonard B, Maes M. Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev 2012; 36(2): 764-85.
[http://dx.doi.org/10.1016/j.neubiorev.2011.12.005 ] [PMID: 22197082]
[16]
Kumar A, Datusalia AK. Metabolic stress and inflammation: Implication in treatment for neurological disorders. CNS Neurol Disord Drug Targets 2018; 17(9): 642-3.
[http://dx.doi.org/10.2174/187152731709180926121555 ] [PMID: 30411678]
[17]
Li X, Chauhan A, Sheikh AM, et al. Elevated immune response in the brain of autistic patients. J Neuroimmunol 2009; 207(1-2): 111-6.
[http://dx.doi.org/10.1016/j.jneuroim.2008.12.002] [PMID: 19157572]
[18]
Wei H, Zou H, Sheikh AM, et al. IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J Neuroinflammation 2011; 8: 52.
[http://dx.doi.org/10.1186/1742-2094-8-52] [PMID: 21595886]
[19]
Bjørklund G, Saad K, Chirumbolo S, et al. Immune dysfunction and neuroinflammation in autism spectrum disorder. Acta Neurobiol Exp (Warsz) 2016; 76(4): 257-68.
[http://dx.doi.org/10.21307/ane-2017-025] [PMID: 28094817]
[20]
Braunschweig D, Duncanson P, Boyce R, et al. Behavioral correlates of maternal antibody status among children with autism. J Autism Dev Disord 2012; 42(7): 1435-45.
[http://dx.doi.org/10.1007/s10803-011-1378-7] [PMID: 22012245]
[21]
Zimmerman AW, Connors SL, Matteson KJ, et al. Maternal antibrain antibodies in autism. Brain Behav Immun 2007; 21(3): 351-7.
[http://dx.doi.org/10.1016/j.bbi.2006.08.005] [PMID: 17029701]
[22]
Dalton P, Deacon R, Blamire A, et al. Maternal neuronal antibodies associated with autism and a language disorder. Ann Neurol 2003; 53(4): 533-7.
[http://dx.doi.org/10.1002/ana.10557] [PMID: 12666123]
[23]
Ashwood P, Anthony A, Torrente F, Wakefield AJ. Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: Mucosal immune activation and reduced counter regulatory interleukin-10. J Clin Immunol 2004; 24(6): 664-73.
[http://dx.doi.org/10.1007/s10875-004-6241-6] [PMID: 15622451]
[24]
Ormstad H, Bryn V, Saugstad OD, Skjeldal O, Maes M. Role of the immune system in Autism Spectrum Disorders (ASD). CNS Neurol Disord Drug Targets 2018; 17(7): 489-95.
[http://dx.doi.org/10.2174/1871527317666180706123229 ] [PMID: 29984670]
[25]
Ashwood P, Enstrom A, Krakowiak P, et al. Decreased transforming growth factor β1 in autism: A potential link between immune dysregulation and impairment in clinical behavioral outcomes. J Neuroimmunol 2008; 204(1-2): 149-53.
[http://dx.doi.org/10.1016/j.jneuroim.2008.07.006] [PMID: 18762342]
[26]
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 2011; 25(1): 40-5.
[http://dx.doi.org/10.1016/j.bbi.2010.08.003] [PMID: 20705131]
[27]
Ashwood P, Wakefield AJ. Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J Neuroimmunol 2006; 173(1-2): 126-34.
[http://dx.doi.org/10.1016/j.jneuroim.2005.12.007] [PMID: 16494951]
[28]
Jyonouchi H, Sun S, Le H. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J Neuroimmunol 2001; 120(1-2): 170-9.
[http://dx.doi.org/10.1016/S0165-5728(01)00421-0 ] [PMID: 11694332]
[29]
Bilbo SD, Schwarz JM. The immune system and developmental programming of brain and behavior. Front Neuroendocrinol 2012; 33(3): 267-86.
[http://dx.doi.org/10.1016/j.yfrne.2012.08.006] [PMID: 22982535]
[30]
Enstrom AM, Lit L, Onore CE, et al. Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain Behav Immun 2009; 23(1): 124-33.
[http://dx.doi.org/10.1016/j.bbi.2008.08.001] [PMID: 18762240]
[31]
Molloy CA, Morrow AL, Meinzen-Derr J, et al. Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol 2006; 172(1-2): 198-205.
[http://dx.doi.org/10.1016/j.jneuroim.2005.11.007] [PMID: 16360218]
[32]
Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005; 57(1): 67-81.
[http://dx.doi.org/10.1002/ana.20315] [PMID: 15546155]
[33]
Zimmerman AW, Jyonouchi H, Comi AM, et al. Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr Neurol 2005; 33(3): 195-201.
[http://dx.doi.org/10.1016/j.pediatrneurol.2005.03.014 ] [PMID: 16139734]
[34]
Croonenberghs J, Bosmans E, Deboutte D, Kenis G, Maes M. Activation of the inflammatory response system in autism. Neuropsychobiology 2002; 45(1): 1-6.
[http://dx.doi.org/10.1159/000048665] [PMID: 11803234]
[35]
Morgan JT, Chana G, Pardo CA, et al. Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biol Psychiatry 2010; 68(4): 368-76.
[http://dx.doi.org/10.1016/j.biopsych.2010.05.024] [PMID: 20674603]
[36]
Suzuki K, Sugihara G, Ouchi Y, et al. Microglial activation in young adults with autism spectrum disorder. JAMA Psychiatry 2013; 70(1): 49-58.
[http://dx.doi.org/10.1001/jamapsychiatry.2013.272 ] [PMID: 23404112]
[37]
Masi A, Breen EJ, Alvares GA, et al. Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder. Mol Autism 2017; 8: 63.
[http://dx.doi.org/10.1186/s13229-017-0176-2] [PMID: 29214007]
[38]
Masi A, Glozier N, Dale R, Guastella AJ. The immune system, cytokines, and biomarkers in autism spectrum disorder. Neurosci Bull 2017; 33(2): 194-204.
[http://dx.doi.org/10.1007/s12264-017-0103-8] [PMID: 28238116]
[39]
Van Lint P, Libert C. Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation. J Leukoc Biol 2007; 82(6): 1375-81.
[http://dx.doi.org/10.1189/jlb.0607338] [PMID: 17709402]
[40]
Mohamed E, Gohary T, Abd E, Aziz N, Darweesh M, Shukery E. Plasma level of transforming growth factor β 1 in children with autism spectrum disorder. Egy J Ear Nose Throat Allied Sci 2015; 16: 69.
[http://dx.doi.org/10.1016/j.ejenta.2014.12.002]
[41]
Fernandes A, Miller-Fleming L, Pais TF. Microglia and inflammation: Conspiracy, controversy or control? Cell Mol Life Sci 2014; 71(20): 3969-85.
[http://dx.doi.org/10.1007/s00018-014-1670-8] [PMID: 25008043]
[42]
Nadeem A, Ahmad SF, Attia SM, Bakheet SA, Al-Harbi NO, Al-Ayadhi LY. Activation of IL-17 receptor leads to increased oxidative inflammation in peripheral monocytes of autistic children. Brain Behav Immun 2018; 67: 335-44.
[http://dx.doi.org/10.1016/j.bbi.2017.09.010] [PMID: 28935156]
[43]
Enstrom AM, Onore CE, Van de Water JA, Ashwood P. Differential monocyte responses to TLR ligands in children with autism spectrum disorders. Brain Behav Immun 2010; 24(1): 64-71.
[http://dx.doi.org/10.1016/j.bbi.2009.08.001] [PMID: 19666104]
[44]
Vojdani A, Mumper E, Granpeesheh D, et al. Low natural killer cell cytotoxic activity in autism: The role of glutathione, IL-2 and IL-15. J Neuroimmunol 2008; 205(1-2): 148-54.
[http://dx.doi.org/10.1016/j.jneuroim.2008.09.005] [PMID: 18929414]
[45]
Warren RP, Foster A, Margaretten NC. Reduced natural killer cell activity in autism. J Am Acad Child Adolesc Psychiatry 1987; 26(3): 333-5.
[http://dx.doi.org/10.1097/00004583-198705000-00008 ] [PMID: 3597287]
[46]
Schleinitz N, Vély F, Harlé JR, Vivier E. Natural killer cells in human autoimmune diseases. Immunology 2010; 131(4): 451-8.
[http://dx.doi.org/10.1111/j.1365-2567.2010.03360.x ] [PMID: 21039469]
[47]
Meltzer A, Van de Water J. The role of the immune system in autism spectrum disorder. Neuropsychopharmacology 2017; 42(1): 284-98.
[http://dx.doi.org/10.1038/npp.2016.158] [PMID: 27534269]
[48]
Stubbs EG, Crawford ML. Depressed lymphocyte responsiveness in autistic children. J Autism Child Schizophr 1977; 7(1): 49-55.
[http://dx.doi.org/10.1007/BF01531114] [PMID: 139400]
[49]
Denney DR, Frei BW, Gaffney GR. Lymphocyte subsets and interleukin-2 receptors in autistic children. J Autism Dev Disord 1996; 26(1): 87-97.
[http://dx.doi.org/10.1007/BF02276236] [PMID: 8819772]
[50]
Ahmad SF, Nadeem A, Ansari MA, et al. Imbalance between the anti- and pro-inflammatory milieu in blood leukocytes of autistic children. Mol Immunol 2017; 82: 57-65.
[http://dx.doi.org/10.1016/j.molimm.2016.12.019] [PMID: 28027499]
[51]
Gupta S, Aggarwal S, Rashanravan B, Lee T. Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism. J Neuroimmunol 1998; 85(1): 106-9.
[http://dx.doi.org/10.1016/S0165-5728(98)00021-6] [PMID: 9627004]
[52]
Engstrom H, Ohlson S, Stubbs E, Maciulis A, Caldwell V, Odell J. Decreased expression of CD95 (FAS/APO-1) on CD4+ T-lymphocytes from participants with Autism. J Dev Phys Disabil 2003; 15: 155-63.
[http://dx.doi.org/10.1023/A:1022827417414]
[53]
Joller N, Peters A, Anderson A, Kuchroo V. Immune checkpoints in CNS autoimmunity. Immunol Rev 2012; 248: 122-39.
[http://dx.doi.org/10.1111/j.1600-065X.2012.01136.x ] [PMID: 22725958]
[54]
Siegel RM, Fleisher TA. The role of Fas and related death receptors in autoimmune and other disease states. J Allergy Clin Immunol 1999; 103(5 Pt 1): 729-38.
[http://dx.doi.org/10.1016/S0091-6749(99)70412-4 ] [PMID: 10329802]
[55]
Dugas B, Renauld JC, Pène J, et al. Interleukin-9 potentiates the interleukin-4-induced immunoglobulin (IgG, IgM and IgE) production by normal human B lymphocytes. Eur J Immunol 1993; 23(7): 1687-92.
[http://dx.doi.org/10.1002/eji.1830230743] [PMID: 7686859]
[56]
Petit-Frere C, Dugas B, Braquet P, Mencia-Huerta JM. Interleukin-9 potentiates the interleukin-4-induced IgE and IgG1 release from murine B lymphocytes. Immunology 1993; 79(1): 146-51.
[PMID: 8509135]
[57]
Chang CH, Wade MG, Stoffregen TA, Hsu CY, Pan CY. Visual tasks and postural sway in children with and without autism spectrum disorders. Res Dev Disabil 2010; 31(6): 1536-42.
[http://dx.doi.org/10.1016/j.ridd.2010.06.003] [PMID: 20598853]
[58]
Angkasekwinai P, Chang SH, Thapa M, Watarai H, Dong C. Regulation of IL-9 expression by IL-25 signaling. Nat Immunol 2010; 11(3): 250-6.
[http://dx.doi.org/10.1038/ni.1846] [PMID: 20154671]
[59]
Heuer L, Ashwood P, Schauer J, et al. Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms. Autism Res 2008; 1(5): 275-83.
[http://dx.doi.org/10.1002/aur.42] [PMID: 19343198]
[60]
Sweeten TL, Posey DJ, McDougle CJ. High blood monocyte counts and neopterin levels in children with autistic disorder. Am J Psychiatry 2003; 160(9): 1691-3.
[http://dx.doi.org/10.1176/appi.ajp.160.9.1691] [PMID: 12944347]
[61]
Connolly AM, Chez MG, Pestronk A, Arnold ST, Mehta S, Deuel RK. Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders. J Pediatr 1999; 134(5): 607-13.
[http://dx.doi.org/10.1016/S0022-3476(99)70248-9 ] [PMID: 10228297]
[62]
Connolly AM, Chez M, Streif EM, et al. Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy. Biol Psychiatry 2006; 59(4): 354-63.
[http://dx.doi.org/10.1016/j.biopsych.2005.07.004] [PMID: 16181614]
[63]
Goines PE, Croen LA, Braunschweig D, et al. Increased midgestational IFN-, IL-4 and IL-5 in women bearing a child with autism: A case-control study. Mol Autism 2011; 2(1): 13.
[http://dx.doi.org/10.1186/2040-2392-2-13] [PMID: 21810230]
[64]
Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral D, Van de Water J. Autoantibodies in Autism Spectrum Disorders (ASD). Ann N Y Acad Sci 2007; 1107: 79-91.
[http://dx.doi.org/10.1196/annals.1381.009] [PMID: 17804535]
[65]
Cabanlit M, Wills S, Goines P, Ashwood P, Van de Water J. Brain-specific autoantibodies in the plasma of subjects with autistic spectrum disorder. Ann N Y Acad Sci 2007; 1107(1): 92-103.
[http://dx.doi.org/10.1196/annals.1381.010] [PMID: 17804536]
[66]
Onore C, Van de Water J, Ashwood P. Decreased levels of EGF in plasma of children with autism spectrum disorder. Autism Res Treat 2012; 2012: 205362.
[http://dx.doi.org/10.1155/2012/205362] [PMID: 22937258]
[67]
Heuer L, Braunschweig D, Ashwood P, Van de Water J, Campbell DB. Association of a MET genetic variant with autism-associated maternal autoantibodies to fetal brain proteins and cytokine expression. Transl Psychiatry 2011; 1: e48.
[http://dx.doi.org/10.1038/tp.2011.48] [PMID: 22833194]
[68]
Brimberg L, Sadiq A, Gregersen PK, Diamond B. Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder. Mol Psychiatry 2013; 18(11): 1171-7.
[http://dx.doi.org/10.1038/mp.2013.101] [PMID: 23958959]
[69]
Nordahl CW, Braunschweig D, Iosif AM, et al. Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder. Brain Behav Immun 2013; 30: 61-5.
[http://dx.doi.org/10.1016/j.bbi.2013.01.084] [PMID: 23395715]
[70]
Akum BF, Chen M, Gunderson SI, Riefler GM, Scerri-Hansen MM, Firestein BL. Cypin regulates dendrite patterning in hippocampal neurons by promoting microtubule assembly. Nat Neurosci 2004; 7(2): 145-52.
[http://dx.doi.org/10.1038/nn1179] [PMID: 14730308]
[71]
Lopes MH, Hajj GN, Muras AG, et al. Interaction of cellular prion and stress-inducible protein 1 promotes neuritogenesis and neuroprotection by distinct signaling pathways. J Neurosci 2005; 25(49): 11330-9.
[http://dx.doi.org/10.1523/JNEUROSCI.2313-05.2005 ] [PMID: 16339028]
[72]
Charrier E, Reibel S, Rogemond V, Aguera M, Thomasset N, Honnorat J. Collapsin Response Mediator Proteins (CRMPs): Involvement in nervous system development and adult neurodegenerative disorders. Mol Neurobiol 2003; 28(1): 51-64.
[http://dx.doi.org/10.1385/MN:28:1:51] [PMID: 14514985]
[73]
Diamond B, Honig G, Mader S, Brimberg L, Volpe BT. Brain-reactive antibodies and disease. Annu Rev Immunol 2013; 31: 345-85.
[http://dx.doi.org/10.1146/annurev-immunol-020711-075041 ] [PMID: 23516983]
[74]
Bauman MD, Iosif AM, Ashwood P, et al. Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey. Transl Psychiatry 2013; 3: e278.
[http://dx.doi.org/10.1038/tp.2013.47] [PMID: 23838889]
[75]
Martínez-Cerdeño V, Maezawa I, Jin L. Dendrites in autism spectrum disorders. Dendrites 2016; pp. 525-43.
[http://dx.doi.org/10.1007/978-4-431-56050-0_20]
[76]
Suzuki K, Matsuzaki H, Iwata K, et al. Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders. PLoS One 2011; 6(5): e20470.
[http://dx.doi.org/10.1371/journal.pone.0020470] [PMID: 21647375]
[77]
Ricci S, Businaro R, Ippoliti F, et al. Altered cytokine and BDNF levels in autism spectrum disorder. Neurotox Res 2013; 24(4): 491-501.
[http://dx.doi.org/10.1007/s12640-013-9393-4] [PMID: 23604965]
[78]
Chez MG, Dowling T, Patel PB, Khanna P, Kominsky M. Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol 2007; 36(6): 361-5.
[http://dx.doi.org/10.1016/j.pediatrneurol.2007.01.012 ] [PMID: 17560496]
[79]
Goshen I, Kreisel T, Ounallah-Saad H, et al. A dual role for interleukin-1 in hippocampal-dependent memory processes. Psychoneuroendocrinology 2007; 32(8-10): 1106-15.
[http://dx.doi.org/10.1016/j.psyneuen.2007.09.004] [PMID: 17976923]
[80]
Labrousse VF, Costes L, Aubert A, et al. Impaired interleukin-1beta and c-Fos expression in the hippocampus is associated with a spatial memory deficit in P2X(7) receptor-deficient mice. PLoS One 2009; 4(6): e6006.
[http://dx.doi.org/10.1371/journal.pone.0006006] [PMID: 19547756]
[81]
Patterson PH. Immune involvement in schizophrenia and autism: Etiology, pathology and animal models. Behav Brain Res 2009; 204(2): 313-21.
[http://dx.doi.org/10.1016/j.bbr.2008.12.016] [PMID: 19136031]
[82]
Bilbo SD. Early-life infection is a vulnerability factor for aging-related glial alterations and cognitive decline. Neurobiol Learn Mem 2010; 94(1): 57-64.
[http://dx.doi.org/10.1016/j.nlm.2010.04.001] [PMID: 20388544]
[83]
Ashwood P, Wills S, Van de Water J. The immune response in autism: A new frontier for autism research. J Leukoc Biol 2006; 80(1): 1-15.
[http://dx.doi.org/10.1189/jlb.1205707] [PMID: 16698940]
[84]
Xie J, Huang L, Li X, et al. Immunological cytokine profiling identifies TNF-α as a key molecule dysregulated in autistic children. Oncotarget 2017; 8(47): 82390-8.
[http://dx.doi.org/10.18632/oncotarget.19326] [PMID: 29137272]
[85]
Li L, Kim J, Boussiotis VA. IL-1β-mediated signals preferentially drive conversion of regulatory T cells but not conventional T cells into IL-17-producing cells. J Immunol 2010; 185(7): 4148-53.
[http://dx.doi.org/10.4049/jimmunol.1001536] [PMID: 20817874]
[86]
Bickel M. The role of interleukin-8 in inflammation and mechanisms of regulation. J Periodontol 1993; 64(5): 456-60.
[PMID: 8315568]
[87]
Inga JMC, Morales CLM, Vera CH, et al. Peripheral inflammatory markers contributing to comorbidities in autism. Behav Sci 2016; 6(4): 29.
[http://dx.doi.org/10.3390/bs6040029] [PMID: 27983615]
[88]
Guloksuz SA, Abali O, Aktas Cetin E, et al. Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders. Br J Psychiatry 2017; 39(3): 195-200.
[http://dx.doi.org/10.1590/1516-4446-2015-1843] [PMID: 28099628]
[89]
Eftekharian MM, Ghafouri-Fard S, Noroozi R, et al. Cytokine profile in autistic patients. Cytokine 2018; 108: 120-6.
[http://dx.doi.org/10.1016/j.cyto.2018.03.034] [PMID: 29602155]
[90]
Krakowiak P, Goines PE, Tancredi DJ, et al. Neonatal cytokine profiles associated with autism spectrum disorder. Biol Psychiatry 2017; 81(5): 442-51.
[http://dx.doi.org/10.1016/j.biopsych.2015.08.007] [PMID: 26392128]
[91]
Hughes HK, Mills KE, Rose D, Ashwood P. Immune dysfunction and autoimmunity as pathological mechanisms in autism spectrum disorders. Front Cell Neurosci 2018; 12: 405.
[http://dx.doi.org/10.3389/fncel.2018.00405] [PMID: 30483058]
[92]
Paolicelli RC, Bolasco G, Pagani F, et al. Synaptic pruning by microglia is necessary for normal brain development. Science 2011; 333(6048): 1456-8.
[http://dx.doi.org/10.1126/science.1202529] [PMID: 21778362]
[93]
Tremblay MÈ, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A. The role of microglia in the healthy brain. J Neurosci 2011; 31(45): 16064-9.
[http://dx.doi.org/10.1523/JNEUROSCI.4158-11.2011 ] [PMID: 22072657]
[94]
Schafer DP, Lehrman EK, Kautzman AG, et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 2012; 74(4): 691-705.
[http://dx.doi.org/10.1016/j.neuron.2012.03.026] [PMID: 22632727]
[95]
Kim SH, Lord C. New autism diagnostic interview-revised algorithms for toddlers and young preschoolers from 12 to 47 months of age. J Autism Dev Disord 2012; 42(1): 82-93.
[http://dx.doi.org/10.1007/s10803-011-1213-1] [PMID: 21384244]
[96]
Salter MW, Stevens B. Microglia emerge as central players in brain disease. Nat Med 2017; 23(9): 1018-27.
[http://dx.doi.org/10.1038/nm.4397] [PMID: 28886007]
[97]
Wolf SA, Boddeke HW, Kettenmann H. Microglia in physiology and disease. Annu Rev Physiol 2017; 79: 619-43.
[http://dx.doi.org/10.1146/annurev-physiol-022516-034406 ] [PMID: 27959620]
[98]
Schafer DP, Stevens B. Microglia function in central nervous system development and plasticity. Cold Spring Harb Perspect Biol 2015; 7(10): a020545.
[http://dx.doi.org/10.1101/cshperspect.a020545] [PMID: 26187728]
[99]
Weinhard L, di Bartolomei G, Bolasco G, et al. Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction. Nat Commun 2018; 9(1): 1228.
[http://dx.doi.org/10.1038/s41467-018-03566-5] [PMID: 29581545]
[100]
Miyamoto A, Wake H, Ishikawa AW, et al. Microglia contact induces synapse formation in developing somatosensory cortex. Nat Commun 2016; 7: 12540.
[http://dx.doi.org/10.1038/ncomms12540] [PMID: 27558646]
[101]
Thion MS, Ginhoux F, Garel S. Microglia and early brain development: An intimate journey. Science 2018; 362(6411): 185-9.
[http://dx.doi.org/10.1126/science.aat0474] [PMID: 30309946]
[102]
Tetreault NA, Hakeem AY, Jiang S, et al. Microglia in the cerebral cortex in autism. J Autism Dev Disord 2012; 42(12): 2569-84.
[http://dx.doi.org/10.1007/s10803-012-1513-0] [PMID: 22466688]
[103]
Patel AB, Tsilioni I, Leeman SE, Theoharides TC. Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism. Proc Natl Acad Sci USA 2016; 113(45): E7049-58.
[http://dx.doi.org/10.1073/pnas.1604992113] [PMID: 27663735]
[104]
Kalkman HO, Feuerbach D. Microglia M2A polarization as potential link between food allergy and autism spectrum disorders. Pharmaceuticals 2017; 10(4)E95
[http://dx.doi.org/10.3390/ph10040095] [PMID: 29232822]
[105]
Pareek V, Nath B, Roy PK. Role of neuroimaging modality in the assessment of oxidative stress in brain: A comprehensive review. CNS Neurol Disord Drug Targets 2019; 18(5): 372-81.
[http://dx.doi.org/10.2174/1871527318666190507102340 ] [PMID: 31580247]
[106]
Smith SE, Li J, Garbett K, Mirnics K, Patterson PH. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci 2007; 27(40): 10695-702.
[http://dx.doi.org/10.1523/JNEUROSCI.2178-07.2007 ] [PMID: 17913903]
[107]
Melnyk S, Fuchs GJ, Schulz E, et al. Metabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism. J Autism Dev Disord 2012; 42(3): 367-77.
[http://dx.doi.org/10.1007/s10803-011-1260-7] [PMID: 21519954]
[108]
Suematsu N, Tsutsui H, Wen J, et al. Oxidative stress mediates tumor necrosis factor-alpha-induced mitochondrial DNA damage and dysfunction in cardiac myocytes. Circulation 2003; 107(10): 1418-23.
[http://dx.doi.org/10.1161/01.CIR.0000055318.09997.1F ] [PMID: 12642364]
[109]
Samavati L, Lee I, Mathes I, Lottspeich F, Hüttemann M. Tumor necrosis factor alpha inhibits oxidative phosphorylation through tyrosine phosphorylation at subunit I of cytochrome c oxidase. J Biol Chem 2008; 283(30): 21134-44.
[http://dx.doi.org/10.1074/jbc.M801954200] [PMID: 18534980]
[110]
Voloboueva LA, Giffard RG. Inflammation, mitochondria, and the inhibition of adult neurogenesis. J Neurosci Res 2011; 89(12): 1989-96.
[http://dx.doi.org/10.1002/jnr.22768] [PMID: 21910136]
[111]
Kumar A, Dhawan A, Kadam A, Shinde A. Autophagy and mitochondria: Targets in neurodegenerative disorders. CNS Neurol Disord Drug Targets 2018; 17(9): 696-705.
[http://dx.doi.org/10.2174/1871527317666180816100203 ] [PMID: 30113005]
[112]
Murphy AJ, Guyre PM, Pioli PA. Estradiol suppresses NF-kappa B activation through coordinated regulation of let-7a and miR-125b in primary human macrophages. J Immunol 2010; 184(9): 5029-37.
[http://dx.doi.org/10.4049/jimmunol.0903463] [PMID: 20351193]
[113]
Shimada K, Crother TR, Karlin J, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 2012; 36(3): 401-14.
[http://dx.doi.org/10.1016/j.immuni.2012.01.009] [PMID: 22342844]
[114]
Lampropoulou V, Sergushichev A, Bambouskova M, et al. Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab 2016; 24(1): 158-66.
[http://dx.doi.org/10.1016/j.cmet.2016.06.004] [PMID: 27374498]
[115]
Bambouskova M, Gorvel L, Lampropoulou V, et al. Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis. Nature 2018; 556(7702): 501-4.
[http://dx.doi.org/10.1038/s41586-018-0052-z] [PMID: 29670287]
[116]
Mills EL, Kelly B, Logan A, et al. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 2016; 167(2): 457-70.
[http://dx.doi.org/10.1016/j.cell.2016.08.064] [PMID: 27667687]
[117]
Mills EL, Ryan DG, Prag HA, et al. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 2018; 556(7699): 113-7.
[http://dx.doi.org/10.1038/nature25986] [PMID: 29590092]
[118]
Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011; 469(7329): 221-5.
[http://dx.doi.org/10.1038/nature09663] [PMID: 21124315]
[119]
Garaude J. Reprogramming of mitochondrial metabolism by innate immunity. Curr Opin Immunol 2019; 56: 17-23.
[http://dx.doi.org/10.1016/j.coi.2018.09.010] [PMID: 30286442]
[120]
Pizzarelli R, Cherubini E. Alterations of GABAergic signaling in autism spectrum disorders. Neural Plast 2011; 2011297153
[http://dx.doi.org/10.1155/2011/297153] [PMID: 21766041]
[121]
Lombard J. Autism: A mitochondrial disorder? Med Hypotheses 1998; 50(6): 497-500.
[http://dx.doi.org/10.1016/S0306-9877(98)90270-5] [PMID: 9710323]
[122]
Legido A, Jethva R, Goldenthal MJ. Mitochondrial dysfunction in autism. Semin Pediatr Neurol 2013; 20(3): 163-75.
[http://dx.doi.org/10.1016/j.spen.2013.10.008] [PMID: 24331358]
[123]
Chauhan A, Gu F, Essa MM, et al. Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism. J Neurochem 2011; 117(2): 209-20.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07189.x ] [PMID: 21250997]
[124]
Tang G, Gutierrez RP, Kuo SH, et al. Mitochondrial abnormalities in temporal lobe of autistic brain. Neurobiol Dis 2013; 54: 349-61.
[http://dx.doi.org/10.1016/j.nbd.2013.01.006] [PMID: 23333625]
[125]
Anitha A, Nakamura K, Thanseem I, et al. Downregulation of the expression of mitochondrial electron transport complex genes in autism brains. Brain Pathol 2013; 23(3): 294-302.
[http://dx.doi.org/10.1111/bpa.12002] [PMID: 23088660]
[126]
Haas RH. Autism and mitochondrial disease. Dev Disabil Res Rev 2010; 16(2): 144-53.
[http://dx.doi.org/10.1002/ddrr.112] [PMID: 20818729]
[127]
Niyazov DM, Kahler SG, Frye RE. Primary mitochondrial disease and secondary mitochondrial dysfunction: Importance of distinction for diagnosis and treatment. Mol Syndromol 2016; 7(3): 122-37.
[http://dx.doi.org/10.1159/000446586] [PMID: 27587988]
[128]
Vali S, Mythri RB, Jagatha B, et al. Integrating glutathione metabolism and mitochondrial dysfunction with implications for Parkinson’s disease: A dynamic model. Neuroscience 2007; 149(4): 917-30.
[http://dx.doi.org/10.1016/j.neuroscience.2007.08.028 ] [PMID: 17936517]
[129]
Shahjadi S, Khan A, Ahmed M. Mitochondrial dysfunction in early diagnosed autism spectrum disorder children. J Dhaka Med Coll 2017; 26(1): 43-7.
[http://dx.doi.org/10.3329/jdmc.v26i1.34000]
[130]
Jiang X, Tang PC, Chen Q, et al. Cordycepin exerts neuroprotective effects via an anti-apoptotic mechanism based on the mitochondrial pathway in a rotenone-induced Parkinsonism rat model. CNS Neurol Disord Drug Targets 2019; 18(8): 609-20.
[http://dx.doi.org/10.2174/1871527318666190905152138 ] [PMID: 31486758]
[131]
Cheng N, Rho JM, Masino SA. Metabolic dysfunction underlying autism spectrum disorder and potential treatment approaches. Front Mol Neurosci 2017; 10: 34.
[http://dx.doi.org/10.3389/fnmol.2017.00034] [PMID: 28270747]
[132]
Hollis F, Kanellopoulos AK, Bagni C. Mitochondrial dysfunction in Autism Spectrum Disorder: Clinical features and perspectives. Curr Opin Neurobiol 2017; 45: 178-87.
[http://dx.doi.org/10.1016/j.conb.2017.05.018] [PMID: 28628841]
[133]
Goldenthal MJ, Damle S, Sheth S, et al. Mitochondrial enzyme dysfunction in autism spectrum disorders; a novel biomarker revealed from buccal swab analysis. Biomarkers Med 2015; 9(10): 957-65.
[http://dx.doi.org/10.2217/bmm.15.72] [PMID: 26439018]
[134]
Hardan AY, Minshew NJ, Melhem NM, et al. An MRI and proton spectroscopy study of the thalamus in children with autism. Psychiatry Res 2008; 163(2): 97-105.
[http://dx.doi.org/10.1016/j.pscychresns.2007.12.002 ] [PMID: 18508243]
[135]
Friedman SD, Shaw DW, Artru AA, et al. Regional brain chemical alterations in young children with autism spectrum disorder. Neurology 2003; 60(1): 100-7.
[http://dx.doi.org/10.1212/WNL.60.1.100] [PMID: 12525726]
[136]
Ipser JC, Syal S, Bentley J, Adnams CM, Steyn B, Stein DJ. 1H-MRS in autism spectrum disorders: A systematic meta-analysis. Metab Brain Dis 2012; 27(3): 275-87.
[http://dx.doi.org/10.1007/s11011-012-9293-y ] [PMID: 22426803]
[137]
Chandrasekaran K, Giordano T, Brady DR, Stoll J, Martin LJ, Rapoport SI. Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease. Brain Res Mol Brain Res 1994; 24(1-4): 336-40.
[http://dx.doi.org/10.1016/0169-328X(94)90147-3 ] [PMID: 7968373]
[138]
Gu F, Chauhan V, Kaur K, et al. Alterations in mitochondrial DNA copy number and the activities of electron transport chain complexes and pyruvate dehydrogenase in the frontal cortex from subjects with autism. Transl Psychiatry 2013; 3e299
[http://dx.doi.org/10.1038/tp.2013.68] [PMID: 24002085]
[139]
Giulivi C, Zhang YF, Omanska-Klusek A, et al. Mitochondrial dysfunction in autism. JAMA 2010; 304(21): 2389-96.
[http://dx.doi.org/10.1001/jama.2010.1706] [PMID: 21119085]
[140]
Ginsberg MR, Rubin RA, Falcone T, Ting AH, Natowicz MR. Brain transcriptional and epigenetic associations with autism. PLoS One 2012; 7(9)e44736
[http://dx.doi.org/10.1371/journal.pone.0044736 ] [PMID: 22984548]
[141]
Weissman JR, Kelley RI, Bauman ML, et al. Mitochondrial disease in autism spectrum disorder patients: A cohort analysis. PLoS One 2008; 3(11)e3815
[http://dx.doi.org/10.1371/journal.pone.0003815] [PMID: 19043581]
[142]
Chen S, Li Z, He Y, et al. Elevated mitochondrial DNA copy number in peripheral blood cells is associated with childhood autism. BMC Psychiatry 2015; 15: 50.
[http://dx.doi.org/10.1186/s12888-015-0432-y] [PMID: 25884388]
[143]
Wang S, Ma F, Huang L, et al. Dl-3-n-Butylphthalide (NBP): A promising therapeutic agent for ischemic stroke. CNS Neurol Disord Drug Targets 2018; 17(5): 338-47.
[http://dx.doi.org/10.2174/1871527317666180612125843 ] [PMID: 29895257]
[144]
Yamano T, Morita S. Effects of pesticides on isolated rat hepatocytes, mitochondria, and microsomes II. Arch Environ Contam Toxicol 1995; 28(1): 1-7.
[http://dx.doi.org/10.1007/BF00213961] [PMID: 7717759]
[145]
Rose S, Melnyk S, Pavliv O, et al. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry 2012; 2e134
[http://dx.doi.org/10.1038/tp.2012.61] [PMID: 22781167]
[146]
Fiorito V, Chiabrando D, Tolosano E. Mitochondrial targeting in neurodegeneration: A heme perspective. Pharmaceuticals 2018; 11(3): 87.
[http://dx.doi.org/10.3390/ph11030087] [PMID: 30231533]
[147]
Yorbik O, Sayal A, Akay C, Akbiyik DI, Sohmen T. Investigation of antioxidant enzymes in children with autistic disorder. Prostaglandins Leukot Essent Fatty Acids 2002; 67(5): 341-3.
[http://dx.doi.org/10.1054/plef.2002.0439] [PMID: 12445495]
[148]
Frye R, Delatorre R, Taylor H, et al. Redox metabolism abnormalities in autistic children associated with mitochondrial disease. Transl Psychiatry 2013; 18e273
[http://dx.doi.org/10.1038/tp.2013.51]
[149]
Zoroglu SS, Armutcu F, Ozen S, et al. Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur Arch Psychiatry Clin Neurosci 2004; 254(3): 143-7.
[http://dx.doi.org/10.1007/s00406-004-0456-7] [PMID: 15205966]
[150]
Arshad N, Lin TS, Yahaya MF. Metabolic syndrome and its effect on the brain: Possible mechanism. CNS Neurol Disord Drug Targets 2018; 17(8): 595-603.
[http://dx.doi.org/10.2174/1871527317666180724143258 ] [PMID: 30047340]
[151]
Ashrafi G, Schwarz TL. The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ 2013; 20(1): 31-42.
[http://dx.doi.org/10.1038/cdd.2012.81] [PMID: 22743996]
[152]
Jansen R, Batista S, Brooks AI, et al. Sex differences in the human peripheral blood transcriptome. BMC Genomics 2014; 15: 33.
[http://dx.doi.org/10.1186/1471-2164-15-33] [PMID: 24438232]
[153]
Dai R, McReynolds S, Leroith T, Heid B, Liang Z, Ahmed SA. Sex differences in the expression of lupus-associated miRNAs in splenocytes from lupus-prone NZB/WF1 mice. Biol Sex Differ 2013; 4(1): 19.
[http://dx.doi.org/10.1186/2042-6410-4-19] [PMID: 24175965]
[154]
Schwarz JM, Bilbo SD. Sex, glia, and development: Interactions in health and disease. Horm Behav 2012; 62(3): 243-53.
[http://dx.doi.org/10.1016/j.yhbeh.2012.02.018] [PMID: 22387107]
[155]
Schneider T, Roman A, Basta-Kaim A, et al. Gender-specific behavioral and immunological alterations in an animal model of autism induced by prenatal exposure to valproic acid. Psychoneuroendocrinology 2008; 33(6): 728-40.
[http://dx.doi.org/10.1016/j.psyneuen.2008.02.011] [PMID: 18396377]
[156]
Nilsen J, Diaz BR. Mechanism of estrogen-mediated neuroprotection: Regulation of mitochondrial calcium and Bcl-2 expression. Proc Natl Acad Sci USA 2003; 100(5): 2842-7.
[http://dx.doi.org/10.1073/pnas.0438041100] [PMID: 12604781]
[157]
Pike CJ. Estrogen modulates neuronal Bcl-xL expression and beta-amyloid-induced apoptosis: Relevance to Alzheimer’s disease. J Neurochem 1999; 72(4): 1552-63.
[http://dx.doi.org/10.1046/j.1471-4159.1999.721552.x ] [PMID: 10098861]
[158]
Singer HS, Morris C, Gause C, Pollard M, Zimmerman AW, Pletnikov M. Prenatal exposure to antibodies from mothers of children with autism produces neurobehavioral alterations: A pregnant dam mouse model. J Neuroimmunol 2009; 211(1-2): 39-48.
[http://dx.doi.org/10.1016/j.jneuroim.2009.03.011] [PMID: 19362378]
[159]
Wise PM, Dubal DB, Wilson ME, Rau SW. Estradiol is a neuroprotective factor in in vivo and in vitro models of brain injury. J Neurocytol 2000; 29(5-6): 401-10.
[http://dx.doi.org/10.1023/A:1007169408561] [PMID: 11424956]
[160]
Yang D, Pelphrey KA, Sukhodolsky DG, et al. Brain responses to biological motion predict treatment outcome in young children with autism. Transl Psychiatry 2016; 6(11)e948
[http://dx.doi.org/10.1038/tp.2016.213] [PMID: 27845779]
[161]
Zhao L, Wu TW, Brinton RD. Estrogen receptor subtypes alpha and beta contribute to neuroprotection and increased Bcl-2 expression in primary hippocampal neurons. Brain Res 2004; 1010(1-2): 22-34.
[http://dx.doi.org/10.1016/j.brainres.2004.02.066] [PMID: 15126114]
[162]
Wang X. The expanding role of mitochondria in apoptosis. Genes Dev 2001; 15(22): 2922-33.
[PMID: 11711427]
[163]
Wang WX, Springer JE. Role of mitochondria in regulating microRNA activity and its relevance to the central nervous system. Neural Regen Res 2015; 10(7): 1026-8.
[http://dx.doi.org/10.4103/1673-5374.160061] [PMID: 26330811]
[164]
Wang X, Sharma RK, Gupta A, et al. Alterations in mitochondria membrane potential and oxidative stress in infertile men: A prospective observational study. Fertil Steril 2003; 80(2): 844-50.
[http://dx.doi.org/10.1016/S0015-0282(03)00983-X ] [PMID: 14505763]
[165]
Anderson G. Daytime orexin and night-time melatonin regulation of mitochondria melatonin: Roles in circadian oscillations systemically and centrally in breast cancer symptomatology. Melatonin Res 2019; 2(4): 1-8.
[http://dx.doi.org/10.32794/mr11250037]
[166]
Anderson G, Rodriguez M, Reiter R. Multiple sclerosis: Melatonin, Orexin, and Ceramide interact with platelet activation coagulation factors and gut-microbiome-derived butyrate in the circadian dysregulation of mitochondria in Glia and immune cells. Int J mol scien 2019; 20(21) 5500
[167]
Maes M, Anderson G, Betancort MSR, Seo M, Ojala JO. Integrating Autism Spectrum Disorder pathophysiology: Mitochondria, Vitamin A, CD38, Oxytocin, Serotonin and Melatonergic alterations in the placenta and gut. Curr Pharm Des 2019; 25(41): 4405-20.
[http://dx.doi.org/10.2174/1381612825666191102165459 ] [PMID: 31682209]
[168]
Anderson G. Integrating pathophysiology in migraine: Role of the gut microbiome and melatonin. Curr Pharm Des 2019; 25(33): 3550-62.
[http://dx.doi.org/10.2174/1381612825666190920114611 ] [PMID: 31538885]
[169]
Anderson G. Gut dysbiosis dysregulates central and systemic homeostasis via decreased melatonin and suboptimal mitochondria functioning: Pathoetiological and pathophysiological implications. Melatonin Res 2019; 2(2): 70-85.
[http://dx.doi.org/10.32794/mr11250022]
[170]
Jin CJ, Engstler AJ, Sellmann C, et al. Sodium butyrate protects mice from the development of the early signs of non-alcoholic fatty liver disease: Role of melatonin and lipid peroxidation. Br J Nutr 2016; 116(10): 1-12.
[http://dx.doi.org/10.1017/S0007114516004025] [PMID: 27876107]
[171]
Erdman SE, Poutahidis T. Microbes and Oxytocin: Benefits for host physiology and behavior. Int Rev Neurobiol 2016; 131: 91-126.
[http://dx.doi.org/10.1016/bs.irn.2016.07.004] [PMID: 27793228]
[172]
Anderson G, Betancort S. Autism Spectrum Disorders: Role of preand post-natal Gamma Delta (γδ) T Cells and immune regulation current pharmaceutical design 2019.
[173]
Togher KL, Kenny LC, O’Keeffe GW. Class-specific histone deacetylase inhibitors promote 11-Beta hydroxysteroid dehydrogenase Type 2 expression in JEG-3 Cells. Int J Cell Biol 2017; 20176169310
[http://dx.doi.org/10.1155/2017/6169310] [PMID: 28321257]
[174]
Alzghoul L. Role of Vitamin D in Autism Spectrum Disorder. Curr Pharm Des 2019; 25(41): 4357-67.
[http://dx.doi.org/10.2174/1381612825666191122092215 ] [PMID: 31755381]
[175]
Seo M, Anderson G. Gut-Amygdala interactions in autism spectrum disorders: Developmental roles via regulating mitochondria, exosomes, immunity and microRNAs. Curr Pharm Des 2019; 25(41): 4344-56.
[http://dx.doi.org/10.2174/1381612825666191105102545 ] [PMID: 31692435]
[176]
Naviaux RK. Antipurinergic therapy for autism-an in-depth review. Mitochondrion 2018; 43: 1-15.
[http://dx.doi.org/10.1016/j.mito.2017.12.007] [PMID: 29253638]
[177]
Pacheva I, Ivanov I. Targeted biomedical treatment for autism spectrum disorders. Curr Pharm Des 2019; 25(41): 4430-53.
[http://dx.doi.org/10.2174/1381612825666191205091312 ] [PMID: 31801452]
[178]
Anderson G, Maes M. Redox regulation and the autistic spectrum: Role of tryptophan catabolites, immuno-inflammation, autoimmunity and the amygdala. Curr Neuropharmacol 2014; 12(2): 148-67.
[http://dx.doi.org/10.2174/1570159X11666131120223757 ] [PMID: 24669209]
[179]
Abdulamir HA, Abdul-Rasheed OF, Abdulghani EA. Low oxytocin and melatonin levels and their possible role in the diagnosis and prognosis in Iraqi autistic children. Saudi Med J 2016; 37(1): 29-36.
[http://dx.doi.org/10.15537/smj.2016.1.13183] [PMID: 26739971]
[180]
Bordt EA, Smith CJ, Demarest TG, Bilbo SD, Kingsbury MA. Mitochondria, oxytocin, and vasopressin: Unfolding the inflammatory protein response. Neurotox Res 2019; 36(2): 239-56.
[http://dx.doi.org/10.1007/s12640-018-9962-7] [PMID: 30259418]
[181]
Treskatsch S, Shaqura M, Dehe L, et al. Evidence for MOR on cell membrane, sarcoplasmatic reticulum and mitochondria in left ventricular myocardium in rats. Heart Vessels 2016; 31(8): 1380-8.
[http://dx.doi.org/10.1007/s00380-015-0784-8] [PMID: 26686371]
[182]
Anderson G. Pathoetiology and pathophysiology of borderline personality: Role of prenatal factors, gut microbiome, mu- and kappa-opioid receptors in amygdala-PFC interactions. Prog Neuropsychopharmacol Biol Psychiatry 2020; 98109782
[http://dx.doi.org/10.1016/j.pnpbp.2019.109782] [PMID: 31689444]
[183]
Pellissier LP, Gandía J, Laboute T, Becker JAJ, Le Merrer J. μ opioid receptor, social behaviour and autism spectrum disorder: Reward matters. Br J Pharmacol 2018; 175(14): 2750-69.
[http://dx.doi.org/10.1111/bph.13808] [PMID: 28369738]
[184]
Kawase T, Nagasawa M, Ikeda H, Yasuo S, Koga Y, Furuse M. Gut microbiota of mice putatively modifies amino acid metabolism in the host brain. Br J Nutr 2017; 117(6): 775-83.
[http://dx.doi.org/10.1017/S0007114517000678] [PMID: 28393748]
[185]
Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism- Comparisons to typical children and correlation with autism severity. BMC Gastroenterol 2011; 11: 22.
[http://dx.doi.org/10.1186/1471-230X-11-22] [PMID: 21410934]
[186]
Desbonnet L, Clarke G, Shanahan F, Dinan TG, Cryan JF. Microbiota is essential for social development in the mouse. Mol Psychiatry 2014; 19(2): 146-8.
[http://dx.doi.org/10.1038/mp.2013.65] [PMID: 23689536]
[187]
McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: A meta-analysis. Pediatrics 2014; 133(5): 872-83.
[http://dx.doi.org/10.1542/peds.2013-3995] [PMID: 24777214]
[188]
Jin SM, Youle RJ. The accumulation of misfolded proteins in the mitochondrial matrix is sensed by PINK1 to induce PARK2/Parkin-mediated mitophagy of polarized mitochondria. Autophagy 2013; 9(11): 1750-7.
[http://dx.doi.org/10.4161/auto.26122] [PMID: 24149988]

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