{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T12:03:08Z","timestamp":1772539388344,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["075-10-2021-113"],"award-info":[{"award-number":["075-10-2021-113"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammation plays a considerable role in the pathogenesis of many diseases, including neurodegenerative and psychiatric ones. Elucidation of the specific features of an immune response in various model organisms, and studying the relation of these features with the behavioral phenotype, can improve the understanding of the molecular mechanisms of many psychopathologies. In this work, we focused on BTBR mice, which have a pronounced autism-like behavioral phenotype, elevated levels of oxidative-stress markers, an abnormal immune response, several structural aberrations in the brain, and other unique traits. Although some studies have already shown an abnormal immune response in BTBR mice, the existing literature data are still fragmentary. Here, we used inflammation induced by low-dose lipopolysaccharide, polyinosinic:polycytidylic acid, or their combinations, in mice of strains BTBR T+Itpr3tf\/J (BTBR) and C57BL6\/J. Peripheral inflammation was assessed by means of a complete blood count, lymphocyte immunophenotyping, and expression levels of cytokines in the spleen. Neuroinflammation was evaluated in the hypothalamus and prefrontal cortex by analysis of mRNA levels of proinflammatory cytokines (tumor necrosis factor, Tnf), (interleukin-1 beta, Il-1\u03b2), and (interleukin-6, Il-6) and of markers of microglia activation (allograft inflammatory factor 1, Aif1) and astroglia activation (glial fibrillary acidic protein, Gfap). We found that in both strains of mice, the most severe inflammatory response was caused by the administration of polyinosinic:polycytidylic acid, whereas the combined administration of the two toll-like receptor (TLR) agonists did not enhance this response. Nonetheless, BTBR mice showed a more pronounced response to low-dose lipopolysaccharide, an altered lymphocytosis ratio due to an increase in the number of CD4+ lymphocytes, and high expression of markers of activated microglia (Aif1) and astroglia (Gfap) in various brain regions as compared to C57BL6\/J mice. Thus, in addition to research into mechanisms of autism-like behavior, BTBR mice can be used as a model of TLR3\/TLR4-induced neuroinflammation and a unique model for finding and evaluating the effectiveness of various TLR antagonists aimed at reducing neuroinflammation.<\/jats:p>","DOI":"10.3390\/ijms232415577","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T01:51:26Z","timestamp":1670550686000},"page":"15577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Unique Features of the Immune Response in BTBR Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Anastasia","family":"Mutovina","sequence":"first","affiliation":[{"name":"Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9722-3037","authenticated-orcid":false,"given":"Kseniya","family":"Ayriyants","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Mezhlumyan","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia","family":"Ryabushkina","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6398-7154","authenticated-orcid":false,"given":"Ekaterina","family":"Litvinova","sequence":"additional","affiliation":[{"name":"Physical Engineering Faculty, Novosibirsk State Technical University, Prospekt Karl Marx, 20, 630073 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5602-5149","authenticated-orcid":false,"given":"Natalia","family":"Bondar","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, Pirogova Street 2, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9281-9002","authenticated-orcid":false,"given":"Julia","family":"Khantakova","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2932-0804","authenticated-orcid":false,"given":"Vasiliy","family":"Reshetnikov","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia"},{"name":"Department of Biotechnology, Sirius University of Science and Technology, 1 Olympic Avenue, 354340 Sochi, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1126\/science.6867729","article-title":"The immune response evokes changes in brain noradrenergic neurons","volume":"221","author":"Besedovsky","year":"1983","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"bqaa055","DOI":"10.1210\/endocr\/bqaa055","article-title":"Neuroendocrine-Immune Crosstalk Shapes Sex-Specific Brain Development","volume":"161","author":"Arambula","year":"2020","journal-title":"Endocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.yfrne.2012.08.006","article-title":"The immune system and developmental programming of brain and behavior","volume":"33","author":"Bilbo","year":"2012","journal-title":"Front. Neuroendocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/npp.2016.158","article-title":"The Role of the Immune System in Autism Spectrum Disorder","volume":"42","author":"Meltzer","year":"2017","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3916","DOI":"10.4049\/jimmunol.173.6.3916","article-title":"Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs","volume":"173","author":"Olson","year":"2004","journal-title":"J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S0165-5728(01)00421-0","article-title":"Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression","volume":"120","author":"Jyonouchi","year":"2001","journal-title":"J. Neuroimmunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neubiorev.2021.07.023","article-title":"Neuroinflammation in autism spectrum disorders: Exercise as a \u201cpharmacological\u201d tool","volume":"129","author":"Toscano","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/ana.20315","article-title":"Neuroglial activation and neuroinflammation in the brain of patients with autism","volume":"57","author":"Vargas","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Khantakova, J.N., Bondar, N., Antontseva, E.V., and Reshetnikov, V.V. (2022). Once induced, it lasts for a long time: The structural and molecular signatures associated with depressive-like behavior after neonatal immune activation. Front. Cell. Neurosci.","DOI":"10.3389\/fncel.2022.1066794"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jneuroim.2019.03.012","article-title":"Toll-like receptors in the pathogenesis of neuroinflammation","volume":"332","author":"Kumar","year":"2019","journal-title":"J. Neuroimmunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bbi.2021.09.009","article-title":"Emerging evidence of Toll-like receptors as a putative pathway linking maternal inflammation and neurodevelopmental disorders in human offspring: A systematic review","volume":"99","author":"Han","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13033","DOI":"10.1523\/JNEUROSCI.4290-06.2007","article-title":"Toll-like receptor 3 is a potent negative regulator of axonal growth in mammals","volume":"27","author":"Cameron","year":"2007","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"169","DOI":"10.15252\/embr.201642586","article-title":"TLR3 downregulates expression of schizophrenia gene Disc1 via MYD88 to control neuronal morphology","volume":"18","author":"Chen","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1083\/jcb.201712113","article-title":"Endosomal TLR3, TLR7, and TLR8 control neuronal morphology through different transcriptional programs","volume":"217","author":"Hung","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13978","DOI":"10.1523\/JNEUROSCI.2140-08.2008","article-title":"Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation","volume":"28","author":"Lathia","year":"2008","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.tins.2011.02.005","article-title":"Toll-like receptor signaling in neural plasticity and disease","volume":"34","author":"Okun","year":"2011","journal-title":"Trends Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/ncb1629","article-title":"Toll-like receptors modulate adult hippocampal neurogenesis","volume":"9","author":"Rolls","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51647","DOI":"10.1074\/jbc.M407328200","article-title":"Neurotoxic effects of lipopolysaccharide on nigral dopaminergic neurons are mediated by microglial activation, interleukin-1beta, and expression of caspase-11 in mice","volume":"279","author":"Arai","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1161\/STROKEAHA.107.498212","article-title":"Toll-like receptor 4 is involved in subacute stress-induced neuroinflammation and in the worsening of experimental stroke","volume":"39","author":"Caso","year":"2008","journal-title":"Stroke"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.bbr.2012.07.021","article-title":"The BTBR T+ tf\/J mouse model for autism spectrum disorders-in search of biomarkers","volume":"251","author":"Meyza","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"113489","DOI":"10.1016\/j.bbr.2021.113489","article-title":"Sex-specific behavioral and structural alterations caused by early-life stress in C57BL\/6 and BTBR mice","volume":"414","author":"Reshetnikov","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4390","DOI":"10.1007\/s12035-016-9977-0","article-title":"Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism","volume":"54","author":"Ahmad","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jneuroim.2008.12.002","article-title":"Elevated immune response in the brain of autistic patients","volume":"207","author":"Li","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.bbi.2014.06.006","article-title":"Inflammatory profiles in the BTBR mouse: How relevant are they to autism spectrum disorders?","volume":"43","author":"Careaga","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Heo, Y., Zhang, Y., Gao, D., Miller, V.M., and Lawrence, D.A. (2011). Aberrant immune responses in a mouse with behavioral disorders. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020912"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1007\/s12035-016-0066-1","article-title":"Resveratrol Ameliorates Dysregulation of Th1, Th2, Th17, and T Regulatory Cell-Related Transcription Factor Signaling in a BTBR T + tf\/J Mouse Model of Autism","volume":"54","author":"Bakheet","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.bbi.2016.05.019","article-title":"C57BL\/6J bone marrow transplant increases sociability in BTBR T(+) Itpr3(tf)\/J mice","volume":"59","author":"Schwartzer","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jones-Davis, D.M., Yang, M., Rider, E., Osbun, N.C., da Gente, G.J., Li, J., Katz, A.M., Weber, M.D., Sen, S., and Crawley, J. (2013). Quantitative trait loci for interhemispheric commissure development and social behaviors in the BTBR T(+) tf\/J mouse model of autism. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061829"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1038\/s41380-020-0685-9","article-title":"Prefrontal cortex circuits in depression and anxiety: Contribution of discrete neuronal populations and target regions","volume":"25","author":"Hare","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/7854_2021_294","article-title":"Inflammation as a Pathophysiologic Pathway to Anhedonia: Mechanisms and Therapeutic Implications","volume":"58","author":"Bekhbat","year":"2022","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_31","first-page":"5","article-title":"Neuroinflammation and depressive disorder: The role of the hypothalamus","volume":"75","author":"Cernackova","year":"2020","journal-title":"J. Clin. Neurosci. Off. J. Neurosurg. Soc. Australas."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.bcp.2018.01.024","article-title":"Hypothalamic inflammation and malfunctioning glia in the pathophysiology of obesity and diabetes: Translational significance","volume":"153","author":"Rahman","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.autneu.2017.09.001","article-title":"Homeostatic systems, biocybernetics, and autonomic neuroscience","volume":"208","author":"Goldstein","year":"2017","journal-title":"Auton. Neurosci. Basic Clin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/s41590-021-01009-w","article-title":"Repositioning TH cell polarization from single cytokines to complex help","volume":"22","author":"Tuzlak","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.neubiorev.2020.05.001","article-title":"Comparison of bacterial lipopolysaccharide-induced sickness behavior in rodents and humans: Relevance for symptoms of anxiety and depression","volume":"115","author":"Lasselin","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"271359","DOI":"10.1155\/2013\/271359","article-title":"Systemic immune activation leads to neuroinflammation and sickness behavior in mice","volume":"2013","author":"Biesmans","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s12974-015-0332-6","article-title":"Systemic inflammation and microglial activation: Systematic review of animal experiments","volume":"12","author":"Hoogland","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1084\/jem.20080091","article-title":"Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5","volume":"205","author":"Kato","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/ni1223","article-title":"Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells","volume":"6","author":"Napolitani","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_42","first-page":"105","article-title":"Systemic Activation of TLR3-Dependent TRIF Signaling Confers Host Defense against Gram-Negative Bacteria in the Intestine","volume":"5","author":"Ruiz","year":"2015","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/80833","article-title":"Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus","volume":"1","author":"Popova","year":"2000","journal-title":"Nat. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41419-018-0520-2","article-title":"Low doses of LPS exacerbate the inflammatory response and trigger death on TLR3-primed human monocytes","volume":"9","author":"Franquesa","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.4049\/jimmunol.178.2.1164","article-title":"MyD88-dependent and MyD88-independent pathways in synergy, priming, and tolerance between TLR agonists","volume":"178","author":"Bagchi","year":"2007","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nn.3599","article-title":"Identification of a unique TGF-beta-dependent molecular and functional signature in microglia","volume":"17","author":"Butovsky","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s12974-016-0644-1","article-title":"Transcriptome sequencing reveals that LPS-triggered transcriptional responses in established microglia BV2 cell lines are poorly representative of primary microglia","volume":"13","author":"Das","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/1742-2094-9-115","article-title":"A comparative review of cell culture systems for the study of microglial biology in Alzheimer\u2019s disease","volume":"9","author":"Stansley","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"R99","DOI":"10.1152\/ajpregu.00087.2021","article-title":"LPS versus Poly I:C model: Comparison of long-term effects of bacterial and viral maternal immune activation on the offspring","volume":"322","author":"Bao","year":"2022","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Khantakova, J.N., Bondar, N.P., Sapronova, A.A., and Reshetnikov, V.V. (2022). Delayed effects of neonatal immune activation on brain neurochemistry and hypothalamic-pituitary-adrenal axis functioning. Eur. J. Neurosci.","DOI":"10.1111\/ejn.15831"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"622614","DOI":"10.3389\/fimmu.2020.622614","article-title":"TLR Agonists as Mediators of Trained Immunity: Mechanistic Insight and Immunotherapeutic Potential to Combat Infection","volume":"11","author":"Owen","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Adhikarla, S.V., Jha, N.K., Goswami, V.K., Sharma, A., Bhardwaj, A., Dey, A., Villa, C., Kumar, Y., and Jha, S.K. (2021). TLR-Mediated Signal Transduction and Neurodegenerative Disorders. Brain Sci., 11.","DOI":"10.3390\/brainsci11111373"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00418-013-1110-0","article-title":"Intermediate filaments are important for astrocyte response to oxidative stress induced by oxygen-glucose deprivation and reperfusion","volume":"140","author":"Nilsson","year":"2013","journal-title":"Histochem. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.pnpbp.2018.09.012","article-title":"Increased oxidative stress in the cerebellum and peripheral immune cells leads to exaggerated autism-like repetitive behavior due to deficiency of antioxidant response in BTBR T+tf\/J mice","volume":"89","author":"Nadeem","year":"2019","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Milatovic, D., Zaja-Milatovic, S., Brockett, M.M., Breyer, R.M., Aschner, M., and Montine, T.J. (2022). Neuroinflammation and oxidative injury in developmental neurotoxicity. Reproductive and Developmental Toxicology, Academic Press. [3rd ed.].","DOI":"10.1016\/B978-0-323-89773-0.00056-4"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.bbi.2006.12.007","article-title":"The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double-stranded RNA (poly I:C)","volume":"21","author":"Cunningham","year":"2007","journal-title":"Brain Behav. Immun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.bbi.2015.04.009","article-title":"Interdependent and independent roles of type I interferons and IL-6 in innate immune, neuroinflammatory and sickness behaviour responses to systemic poly I:C","volume":"48","author":"Murray","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.bbi.2012.11.010","article-title":"Poly I:C-induced activation of the immune response is accompanied by depression and anxiety-like behaviours, kynurenine pathway activation and reduced BDNF expression","volume":"28","author":"Gibney","year":"2013","journal-title":"Brain Behav. Immun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1089\/jir.1997.17.197","article-title":"Early induction of proinflammatory cytokine and type I interferon mRNAs following Newcastle disease virus, poly [rI:rC], or low-dose LPS challenge of the mouse","volume":"17","author":"Majde","year":"1997","journal-title":"J. Interferon Cytokine Res. Off. J. Int. Soc. Interferon Cytokine Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7029726","DOI":"10.1155\/2019\/7029726","article-title":"The Effects of Immunosuppressive Factors on Primary Dendritic Cells from C57BL\/6 and CBA Mice","volume":"2019","author":"Kurilin","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/00000658-198908000-00018","article-title":"Peripheral blood leukocyte kinetics following in vivo lipopolysaccharide (LPS) administration to normal human subjects. Influence of elicited hormones and cytokines","volume":"210","author":"Richardson","year":"1989","journal-title":"Ann. Surg."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"110068","DOI":"10.1016\/j.pnpbp.2020.110068","article-title":"Social defeat stress in adult mice causes alterations in gene expression, alternative splicing, and the epigenetic landscape of H3K4me3 in the prefrontal cortex: An impact of early-life stress","volume":"106","author":"Reshetnikov","year":"2021","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15577\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:36:49Z","timestamp":1760146609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":62,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415577"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415577","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,8]]}}}