The Impact of Neuroimmune Alterations in Autism Spectrum Disorder

Overview

Journal Front Psychiatry

Specialty Psychiatry

Date 2015 Oct 7

PMID 26441683

Citations 50

Authors

Carmem Gottfried

Victorio Bambini-Junior

Fiona Francis

Rudimar Riesgo

Wilson Savino

Affiliations

Soon will be listed here.

Abstract

Autism spectrum disorder (ASD) involves a complex interplay of both genetic and environmental risk factors, with immune alterations and synaptic connection deficiency in early life. In the past decade, studies of ASD have substantially increased, in both humans and animal models. Immunological imbalance (including autoimmunity) has been proposed as a major etiological component in ASD, taking into account increased levels of pro-inflammatory cytokines observed in postmortem brain from patients, as well as autoantibody production. Also, epidemiological studies have established a correlation of ASD with family history of autoimmune diseases; associations with major histocompatibility complex haplotypes and abnormal levels of immunological markers in the blood. Moreover, the use of animal models to study ASD is providing increasing information on the relationship between the immune system and the pathophysiology of ASD. Herein, we will discuss the accumulating literature for ASD, giving special attention to the relevant aspects of factors that may be related to the neuroimmune interface in the development of ASD, including changes in neuroplasticity.

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References

Sweeten T, Posey D, McDougle C . High blood monocyte counts and neopterin levels in children with autistic disorder. Am J Psychiatry. 2003; 160(9):1691-3. DOI: 10.1176/appi.ajp.160.9.1691. View

Vasu M, Anitha A, Thanseem I, Suzuki K, Yamada K, Takahashi T . Serum microRNA profiles in children with autism. Mol Autism. 2014; 5:40. PMC: 4132421. DOI: 10.1186/2040-2392-5-40. View

Zhou B, Liu Y, Kim B, Xiao Y, He J . Astrocyte activation and dysfunction and neuron death by HIV-1 Tat expression in astrocytes. Mol Cell Neurosci. 2004; 27(3):296-305. DOI: 10.1016/j.mcn.2004.07.003. View

Ning Z, Zhao D, Liu H, Yang J, Han C, Cui Y . Altered expression of the prion gene in rat astrocyte and neuron cultures treated with prion peptide 106-126. Cell Mol Neurobiol. 2006; 25(8):1171-83. PMC: 11529221. DOI: 10.1007/s10571-005-8357-5. View

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. DOI: 10.1016/s0165-5728(01)00421-0. View

Sweeten T, Posey D, Shankar S, McDougle C . High nitric oxide production in autistic disorder: a possible role for interferon-gamma. Biol Psychiatry. 2004; 55(4):434-7. DOI: 10.1016/j.biopsych.2003.09.001. View

Coutinho A, Sousa I, Martins M, Correia C, Morgadinho T, Bento C . Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels. Hum Genet. 2007; 121(2):243-56. DOI: 10.1007/s00439-006-0301-3. View

Zimmerman A, Connors S, Matteson K, Lee L, Singer H, Castaneda J . Maternal antibrain antibodies in autism. Brain Behav Immun. 2006; 21(3):351-7. DOI: 10.1016/j.bbi.2006.08.005. View

Li X, Chauhan A, Sheikh A, Patil S, Chauhan V, Li X . Elevated immune response in the brain of autistic patients. J Neuroimmunol. 2009; 207(1-2):111-6. PMC: 2770268. DOI: 10.1016/j.jneuroim.2008.12.002. View

10.

Ashwood P, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen L . Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes. J Neuroimmunol. 2008; 204(1-2):149-53. PMC: 2615583. DOI: 10.1016/j.jneuroim.2008.07.006. View

11.

Campbell D, Buie T, Winter H, Bauman M, Sutcliffe J, Perrin J . Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions. Pediatrics. 2009; 123(3):1018-24. DOI: 10.1542/peds.2008-0819. View

12.

Chez M, Dowling T, Patel P, Khanna P, Kominsky M . Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol. 2007; 36(6):361-5. DOI: 10.1016/j.pediatrneurol.2007.01.012. View

13.

Okada K, Hashimoto K, Iwata Y, Nakamura K, Tsujii M, Tsuchiya K . Decreased serum levels of transforming growth factor-beta1 in patients with autism. Prog Neuropsychopharmacol Biol Psychiatry. 2006; 31(1):187-90. DOI: 10.1016/j.pnpbp.2006.08.020. View

14.

Rathinam M, Watts L, Stark A, Mahimainathan L, Stewart J, Schenker S . Astrocyte control of fetal cortical neuron glutathione homeostasis: up-regulation by ethanol. J Neurochem. 2006; 96(5):1289-300. DOI: 10.1111/j.1471-4159.2006.03674.x. View

15.

Braunschweig D, Van de Water J . Maternal autoantibodies in autism. Arch Neurol. 2012; 69(6):693-9. PMC: 4776649. DOI: 10.1001/archneurol.2011.2506. View

16.

Sakurai T, Reichert J, Hoffman E, Cai G, Jones H, Faham M . A large-scale screen for coding variants in SERT/SLC6A4 in autism spectrum disorders. Autism Res. 2009; 1(4):251-7. PMC: 2678895. DOI: 10.1002/aur.30. View

17.

Besedovsky H, Del Rey A . Immune-neuro-endocrine interactions: facts and hypotheses. Endocr Rev. 1996; 17(1):64-102. DOI: 10.1210/edrv-17-1-64. View

18.

Casanova M . Neuropathological and genetic findings in autism: the significance of a putative minicolumnopathy. Neuroscientist. 2006; 12(5):435-41. DOI: 10.1177/1073858406290375. View

19.

Theoharides T, Stewart J, Panagiotidou S, Melamed I . Mast cells, brain inflammation and autism. Eur J Pharmacol. 2015; 778:96-102. DOI: 10.1016/j.ejphar.2015.03.086. View

20.

Malik M, Sheikh A, Wen G, Spivack W, Brown W, Li X . Expression of inflammatory cytokines, Bcl2 and cathepsin D are altered in lymphoblasts of autistic subjects. Immunobiology. 2010; 216(1-2):80-5. DOI: 10.1016/j.imbio.2010.03.001. View