{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T16:25:09Z","timestamp":1793550309167,"version":"4.5.0"},"reference-count":100,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:00:00Z","timestamp":1670284800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:00:00Z","timestamp":1670284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Ningxia Brain Project","award":["No. 2016BZ07"],"award-info":[{"award-number":["No. 2016BZ07"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82060261"],"award-info":[{"award-number":["No. 82060261"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research Project of Ningxia","award":["No.2018YBZD04917"],"award-info":[{"award-number":["No.2018YBZD04917"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Until now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific brain circuits, has recently been considered as a promising intervention for neuropsychiatric disorders. Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability. Herein, we investigated the effects of continuous high-frequency deep brain stimulation in the anterior insula of rats exposed to VPA and explored cognitive functions, behavior, and molecular proteins connected to autism spectrum disorder.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>VPA-exposed offspring were bilaterally implanted with electrodes in the anterior insula (Day 0) with a recovery period of 1\u00a0week. (Day 0\u20137). High-frequency deep brain stimulation was applied from days 11 to 29. Three behavioral tests, including three-chamber social interaction test, were performed on days 7, 13, 18, 25 and 36, and several rats were used for analysis of immediate early genes and proteomic after deep brain stimulation intervention. Meanwhile, animals were subjected to a 20\u00a0day spatial learning and cognitive rigidity test using IntelliCage on day 11.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Deep brain stimulation improved the sociability and social novelty preference at day 18 prior to those at day 13, and the improvement has reached the upper limit compared to day 25. As for repetitive\/stereotypic-like behavior, self- grooming time were reduced at day 18 and reached the upper limit, and the numbers of burried marbles were reduced at day 13 prior to those at day 18 and day 25. The improvements of sociability and social novelty preference were persistent after the stimulation had ceased. Spatial learning ability and cognitive rigidity were unaffected. We identified 35 proteins in the anterior insula, some of which were intimately linked to autism, and their expression levels were reversed upon administration of deep brain stimulation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Autism-like behavior was ameliorated and autism-related proteins were reversed in the insula by deep brain stimulation intervention, these findings reveal that the insula may be a potential target for DBS in the treatment of autism, which provide a theoretical basis for its clinical application., although future studies are still warranted.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-022-03787-9","type":"journal-article","created":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T08:04:04Z","timestamp":1670313844000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model"],"prefix":"10.1186","volume":"20","author":[{"given":"Lifei","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shucai","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caibin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuicui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhao","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baorui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaofan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anni","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4104-0135","authenticated-orcid":false,"given":"Tao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,6]]},"reference":[{"key":"3787_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41572-019-0138-4","volume":"6","author":"C Lord","year":"2020","unstructured":"Lord C, Brugha TS, Charman T, et al. Autism spectrum disorder. Nat Rev Dis Primers. 2020;6:5.","journal-title":"Nat Rev Dis Primers"},{"key":"3787_CR2","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nrn.2017.112","volume":"18","author":"CE Robertson","year":"2017","unstructured":"Robertson CE, Baron-Cohen S. Sensory perception in autism. Nat Rev Neurosci. 2017;18:671\u201384.","journal-title":"Nat Rev Neurosci"},{"key":"3787_CR3","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1017\/S003329171400172X","volume":"45","author":"AJ Baxter","year":"2015","unstructured":"Baxter AJ, Brugha TS, Erskine HE, et al. The epidemiology and global burden of autism spectrum disorders. Psychol Med. 2015;45:601\u201313.","journal-title":"Psychol Med"},{"key":"3787_CR4","doi-asserted-by":"publisher","first-page":"281","DOI":"10.31887\/DCNS.2012.14.3\/pchaste","volume":"14","author":"P Chaste","year":"2012","unstructured":"Chaste P, Leboyer M. Autism risk factors: genes, environment, and gene-environment interactions. Dialogues Clin Neurosci. 2012;14:281\u201392.","journal-title":"Dialogues Clin Neurosci"},{"key":"3787_CR5","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.pharmthera.2018.05.007","volume":"190","author":"SR Sharma","year":"2018","unstructured":"Sharma SR, Gonda X, Tarazi FI. Autism spectrum disorder: classification, diagnosis and therapy. Pharmacol Ther. 2018;190:91\u2013104.","journal-title":"Pharmacol Ther"},{"key":"3787_CR6","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201809575","author":"M Jakobs","year":"2019","unstructured":"Jakobs M, Fomenko A, Lozano AM, et al. Cellular molecular and clinical mechanisms of action of deep brain stimulation-a systematic review on established indications and outlook on future developments. EMBO Mol Med. 2019. https:\/\/doi.org\/10.15252\/emmm.201809575.","journal-title":"EMBO Mol Med"},{"key":"3787_CR7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1152\/jn.00281.2015","volume":"115","author":"TM Herrington","year":"2016","unstructured":"Herrington TM, Cheng JJ, Eskandar EN. Mechanisms of deep brain stimulation. J Neurophysiol. 2016;115:19\u201338.","journal-title":"J Neurophysiol"},{"key":"3787_CR8","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1056\/NEJMct1208070","volume":"367","author":"MS Okun","year":"2012","unstructured":"Okun MS. Deep-brain stimulation for Parkinson\u2019s disease. N Engl J Med. 2012;367:1529\u201338.","journal-title":"N Engl J Med"},{"key":"3787_CR9","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1002\/mds.25884","volume":"29","author":"KA Pauls","year":"2014","unstructured":"Pauls KA, Hammesfahr S, Moro E, et al. Deep brain stimulation in the ventrolateral thalamus\/subthalamic area in dystonia with head tremor. Mov Disord. 2014;29:953\u20139.","journal-title":"Mov Disord"},{"key":"3787_CR10","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1016\/S0140-6736(21)00794-7","volume":"397","author":"H Knotkova","year":"2021","unstructured":"Knotkova H, Hamani C, Sivanesan E, et al. Neuromodulation for chronic pain. Lancet. 2021;397:2111\u201324.","journal-title":"Lancet"},{"key":"3787_CR11","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41582-018-0128-2","volume":"15","author":"AM Lozano","year":"2019","unstructured":"Lozano AM, Lipsman N, Bergman H, et al. Deep brain stimulation: current challenges and future directions. Nat Rev Neurol. 2019;15:148\u201360.","journal-title":"Nat Rev Neurol"},{"key":"3787_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092840","author":"HF Wu","year":"2018","unstructured":"Wu HF, Chen YJ, Chu MC, et al. Deep brain stimulation modified autism-like deficits via the serotonin system in a valproic acid-induced rat model. Int J Mol Sci. 2018. https:\/\/doi.org\/10.3390\/ijms19092840.","journal-title":"Int J Mol Sci"},{"key":"3787_CR13","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1016\/j.brs.2019.07.004","volume":"12","author":"TC Lin","year":"2019","unstructured":"Lin TC, Lo YC, Lin HC, et al. MR imaging central thalamic deep brain stimulation restored autistic-like social deficits in the rat. Brain Stimul. 2019;12:1410\u201320.","journal-title":"Brain Stimul"},{"key":"3787_CR14","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1038\/npp.2015.350","volume":"41","author":"AD Chang","year":"2016","unstructured":"Chang AD, Berges VA, Chung SJ, et al. High-frequency stimulation at the subthalamic nucleus suppresses excessive self-grooming in autism-like mouse models. Neuropsychopharmacology. 2016;41:1813\u201321.","journal-title":"Neuropsychopharmacology"},{"key":"3787_CR15","doi-asserted-by":"publisher","first-page":"R580","DOI":"10.1016\/j.cub.2017.05.010","volume":"27","author":"N Gogolla","year":"2017","unstructured":"Gogolla N. The insular cortex. Curr Biol. 2017;27:R580-6.","journal-title":"Curr Biol"},{"key":"3787_CR16","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55585","author":"DA Gehrlach","year":"2020","unstructured":"Gehrlach DA, Weiand C, Gaitanos TN, et al. A whole-brain connectivity map of mouse insular cortex. Elife. 2020. https:\/\/doi.org\/10.7554\/eLife.55585.","journal-title":"Elife"},{"key":"3787_CR17","doi-asserted-by":"publisher","first-page":"9878","DOI":"10.1523\/JNEUROSCI.1138-17.2019","volume":"39","author":"WW Seeley","year":"2019","unstructured":"Seeley WW. The salience network: a neural system for perceiving and responding to homeostatic demands. J Neurosci. 2019;39:9878\u201382.","journal-title":"J Neurosci"},{"key":"3787_CR18","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/j.biopsych.2020.06.023","volume":"88","author":"PJ Tsai","year":"2020","unstructured":"Tsai PJ, Keeley RJ, Carmack SA, et al. Converging structural and functional evidence for a rat salience network. Biol Psychiatry. 2020;88:867\u201378.","journal-title":"Biol Psychiatry"},{"key":"3787_CR19","doi-asserted-by":"publisher","first-page":"2472","DOI":"10.1017\/S0033291717000988","volume":"47","author":"M Parellada","year":"2017","unstructured":"Parellada M, Pina-Camacho L, Moreno C, et al. Insular pathology in young people with high-functioning autism and first-episode psychosis. Psychol Med. 2017;47:2472\u201382.","journal-title":"Psychol Med"},{"key":"3787_CR20","doi-asserted-by":"publisher","first-page":"234","DOI":"10.3389\/fnins.2018.00234","volume":"12","author":"J Xu","year":"2018","unstructured":"Xu J, Wang H, Zhang L, et al. Both hypo-connectivity and hyper-connectivity of the insular subregions associated with severity in children with autism spectrum disorders. Front Neurosci. 2018;12:234.","journal-title":"Front Neurosci"},{"key":"3787_CR21","doi-asserted-by":"publisher","first-page":"e3000584","DOI":"10.1371\/journal.pbio.3000584","volume":"18","author":"I Miura","year":"2020","unstructured":"Miura I, Sato M, Overton E, et al. Encoding of social exploration by neural ensembles in the insular cortex. PLoS Biol. 2020;18:e3000584.","journal-title":"PLoS Biol"},{"key":"3787_CR22","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41593-018-0071-y","volume":"21","author":"MM Rogers-Carter","year":"2018","unstructured":"Rogers-Carter MM, Varela JA, Gribbons KB, et al. Insular cortex mediates approach and avoidance responses to social affective stimuli. Nat Neurosci. 2018;21:404\u201314.","journal-title":"Nat Neurosci"},{"key":"3787_CR23","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/sj.npp.1300518","volume":"30","author":"T Schneider","year":"2005","unstructured":"Schneider T, Przew\u0142ocki R. Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology. 2005;30:80\u20139.","journal-title":"Neuropsychopharmacology"},{"key":"3787_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2010.12.018","author":"KC Kim","year":"2010","unstructured":"Kim KC, Kim P, Go HS, et al. The critical period of valproate exposure to induce autistic symptoms in Sprague-Dawley rats. Toxicol Lett. 2010. https:\/\/doi.org\/10.1016\/j.toxlet.2010.12.018.","journal-title":"Toxicol Lett"},{"key":"3787_CR25","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1002\/tera.1420350205","volume":"35","author":"CV Vorhees","year":"1987","unstructured":"Vorhees CV. Teratogenicity and developmental toxicity of valproic acid in rats. Teratology. 1987;35:195\u2013202.","journal-title":"Teratology"},{"key":"3787_CR26","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.expneurol.2017.04.017","volume":"299","author":"C Nicolini","year":"2018","unstructured":"Nicolini C, Fahnestock M. The valproic acid-induced rodent model of autism. Exp Neurol. 2018;299:217\u201327.","journal-title":"Exp Neurol"},{"key":"3787_CR27","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"G Paxinos","year":"2013","unstructured":"Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. London: Academic Press; 2013."},{"key":"3787_CR28","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1002\/mrdd.20039","volume":"10","author":"JN Crawley","year":"2004","unstructured":"Crawley JN. Designing mouse behavioral tasks relevant to autistic-like behaviors. Ment Retard Dev Disabil Res Rev. 2004;10:248\u201358.","journal-title":"Ment Retard Dev Disabil Res Rev"},{"key":"3787_CR29","doi-asserted-by":"publisher","first-page":"146675","DOI":"10.1016\/j.brainres.2020.146675","volume":"1732","author":"EM Hughes","year":"2020","unstructured":"Hughes EM, Calcagno P, Clarke M, et al. Prenatal exposure to valproic acid reduces social responses and alters mRNA levels of opioid receptor and pre-pro-peptide in discrete brain regions of adolescent and adult male rats. Brain Res. 2020;1732:146675.","journal-title":"Brain Res"},{"key":"3787_CR30","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s00213-019-05357-2","volume":"237","author":"S Mohammadi","year":"2020","unstructured":"Mohammadi S, Asadi-Shekaari M, Basiri M, et al. Improvement of autistic-like behaviors in adult rats prenatally exposed to valproic acid through early suppression of NMDA receptor function. Psychopharmacology. 2020;237:199\u2013208.","journal-title":"Psychopharmacology"},{"key":"3787_CR31","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13229-018-0221-9","volume":"9","author":"M Campolongo","year":"2018","unstructured":"Campolongo M, Kazlauskas N, Falasco G, et al. Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment. Mol Autism. 2018;9:36.","journal-title":"Mol Autism"},{"key":"3787_CR32","doi-asserted-by":"publisher","first-page":"112966","DOI":"10.1016\/j.bbr.2020.112966","volume":"397","author":"ZE McKinnell","year":"2021","unstructured":"McKinnell ZE, Maze T, Ramos A, et al. Valproic acid treated female Long-Evans rats are impaired on attentional set-shifting. Behav Brain Res. 2021;397:112966.","journal-title":"Behav Brain Res"},{"key":"3787_CR33","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1093\/jn\/nxy012","volume":"148","author":"J Zheng","year":"2018","unstructured":"Zheng J, Jiang R, Chen M, et al. Multi-copper ferroxidase-deficient mice have increased brain iron concentrations and learning and memory deficits. J Nutr. 2018;148:643\u20139.","journal-title":"J Nutr"},{"key":"3787_CR34","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12993-017-0125-4","volume":"13","author":"N Wu","year":"2017","unstructured":"Wu N, Wang F, Jin Z, et al. Effects of GABA(B) receptors in the insula on recognition memory observed with intellicage. Behav Brain Funct. 2017;13:7.","journal-title":"Behav Brain Funct"},{"key":"3787_CR35","first-page":"140","volume":"8","author":"A Pu\u015bcian","year":"2014","unstructured":"Pu\u015bcian A, L\u0119ski S, G\u00f3rkiewicz T, et al. A novel automated behavioral test battery assessing cognitive rigidity in two genetic mouse models of autism. Front Behav Neurosci. 2014;8:140.","journal-title":"Front Behav Neurosci"},{"key":"3787_CR36","doi-asserted-by":"publisher","first-page":"577155","DOI":"10.3389\/fpsyt.2020.577155","volume":"11","author":"H Chang","year":"2020","unstructured":"Chang H, Gao C, Sun K, et al. Continuous high frequency deep brain stimulation of the rat anterior insula attenuates the relapse post withdrawal and strengthens the extinction of morphine seeking. Front Psychiatry. 2020;11:577155.","journal-title":"Front Psychiatry"},{"key":"3787_CR37","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.ijdevneu.2014.07.006","volume":"38","author":"H Bielas","year":"2014","unstructured":"Bielas H, Arck P, Bruenahl CA, et al. Prenatal stress increases the striatal and hippocampal expression of correlating c-FOS and serotonin transporters in murine offspring. Int J Dev Neurosci. 2014;38:30\u20135.","journal-title":"Int J Dev Neurosci"},{"key":"3787_CR38","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1007\/s12311-016-0812-y","volume":"16","author":"G Huguet","year":"2017","unstructured":"Huguet G, Kadar E, Temel Y, et al. Electrical stimulation normalizes c-Fos expression in the deep cerebellar nuclei of depressive-like rats: implication of antidepressant activity. Cerebellum. 2017;16:398\u2013410.","journal-title":"Cerebellum"},{"key":"3787_CR39","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.nbd.2015.05.007","volume":"80","author":"S Hachem-Delaunay","year":"2015","unstructured":"Hachem-Delaunay S, Fournier ML, Cohen C, et al. Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to cocaine within the reward circuit. Neurobiol Dis. 2015;80:54\u201362.","journal-title":"Neurobiol Dis"},{"key":"3787_CR40","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/j.1749-6632.2011.05990.x","volume":"1225","author":"AD Craig","year":"2011","unstructured":"Craig AD. Significance of the insula for the evolution of human awareness of feelings from the body. Ann N Y Acad Sci. 2011;1225:72\u201382.","journal-title":"Ann N Y Acad Sci"},{"key":"3787_CR41","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/nrn4044","volume":"16","author":"A Etkin","year":"2015","unstructured":"Etkin A, B\u00fcchel C, Gross JJ. The neural bases of emotion regulation. Nat Rev Neurosci. 2015;16:693\u2013700.","journal-title":"Nat Rev Neurosci"},{"key":"3787_CR42","doi-asserted-by":"publisher","first-page":"117655","DOI":"10.1016\/j.lfs.2020.117655","volume":"254","author":"K Sun","year":"2020","unstructured":"Sun K, Xiao L, Wu Y, et al. GABAergic neurons in the insular cortex play an important role in cue-morphine reward memory reconsolidation. Life Sci. 2020;254:117655.","journal-title":"Life Sci"},{"key":"3787_CR43","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/mp.2015.140","volume":"21","author":"A Belin-Rauscent","year":"2016","unstructured":"Belin-Rauscent A, Daniel ML, Puaud M, et al. From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive behavior. Mol Psychiatry. 2016;21:491\u20139.","journal-title":"Mol Psychiatry"},{"key":"3787_CR44","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-022-05471-9","author":"W Zhang","year":"2022","unstructured":"Zhang W, Zhuo S, Li X, et al. Autistic traits and empathy for others; pain among the general population: test of the mediating effects of first-hand pain sensitivity. J Autism Dev Disord. 2022. https:\/\/doi.org\/10.1007\/s10803-022-05471-9.","journal-title":"J Autism Dev Disord"},{"key":"3787_CR45","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1007\/s11920-017-0846-y","volume":"19","author":"V Postorino","year":"2017","unstructured":"Postorino V, Kerns CM, Vivanti G, et al. Anxiety disorders and obsessive-compulsive disorder in individuals with autism spectrum disorder. Curr Psychiatry Rep. 2017;19:92.","journal-title":"Curr Psychiatry Rep"},{"key":"3787_CR46","doi-asserted-by":"publisher","first-page":"110185","DOI":"10.1016\/j.pnpbp.2020.110185","volume":"108","author":"EM Elnahas","year":"2021","unstructured":"Elnahas EM, Abuelezz SA, Mohamad MI, et al. Validation of prenatal versus postnatal valproic acid rat models of autism: a behavioral and neurobiological study. Prog Neuropsychopharmacol Biol Psychiatry. 2021;108:110185.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"3787_CR47","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.neuropharm.2016.04.020","volume":"108","author":"L Jim\u00e9nez-S\u00e1nchez","year":"2016","unstructured":"Jim\u00e9nez-S\u00e1nchez L, Linge R, Campa L, et al. Behavioral, neurochemical and molecular changes after acute deep brain stimulation of the infralimbic prefrontal cortex. Neuropharmacology. 2016;108:91\u2013102.","journal-title":"Neuropharmacology"},{"key":"3787_CR48","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.biopsych.2018.05.011","volume":"84","author":"CM Pinhal","year":"2018","unstructured":"Pinhal CM, van den Boom B, Santana-Kragelund F, et al. Differential effects of deep brain stimulation of the internal capsule and the striatum on excessive grooming in sapap3 mutant mice. Biol Psychiatry. 2018;84:917\u201325.","journal-title":"Biol Psychiatry"},{"key":"3787_CR49","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.expneurol.2009.07.023","volume":"220","author":"AL Jensen","year":"2009","unstructured":"Jensen AL, Durand DM. High frequency stimulation can block axonal conduction. Exp Neurol. 2009;220:57\u201370.","journal-title":"Exp Neurol"},{"key":"3787_CR50","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.nbd.2013.09.006","volume":"62","author":"R Rosenbaum","year":"2014","unstructured":"Rosenbaum R, Zimnik A, Zheng F, et al. Axonal and synaptic failure suppress the transfer of firing rate oscillations, synchrony and information during high frequency deep brain stimulation. Neurobiol Dis. 2014;62:86\u201399.","journal-title":"Neurobiol Dis"},{"key":"3787_CR51","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s00701-006-1058-0","volume":"149","author":"R Xia","year":"2007","unstructured":"Xia R, Berger F, Piallat B, et al. Alteration of hormone and neurotransmitter production in cultured cells by high and low frequency electrical stimulation. Acta Neurochir (Wien). 2007;149:67\u201373.","journal-title":"Acta Neurochir (Wien)"},{"key":"3787_CR52","doi-asserted-by":"publisher","first-page":"869792","DOI":"10.3389\/fnbeh.2022.869792","volume":"16","author":"R Ghahremani","year":"2022","unstructured":"Ghahremani R, Mohammadkhani R, Salehi I, et al. Sex differences in spatial learning and memory in valproic acid rat model of autism: possible beneficial role of exercise interventions. Front Behav Neurosci. 2022;16:869792.","journal-title":"Front Behav Neurosci"},{"key":"3787_CR53","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1038\/npp.2013.274","volume":"39","author":"G Karvat","year":"2014","unstructured":"Karvat G, Kimchi T. Acetylcholine elevation relieves cognitive rigidity and social deficiency in a mouse model of autism. Neuropsychopharmacology. 2014;39:831\u201340.","journal-title":"Neuropsychopharmacology"},{"key":"3787_CR54","doi-asserted-by":"publisher","first-page":"E1032","DOI":"10.1073\/pnas.1714691115","volume":"115","author":"B Suarez-Jimenez","year":"2018","unstructured":"Suarez-Jimenez B, Bisby JA, Horner AJ, et al. Linked networks for learning and expressing location-specific threat. Proc Natl Acad Sci U S A. 2018;115:E1032-40.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3787_CR55","doi-asserted-by":"publisher","first-page":"2176","DOI":"10.3390\/cells9102176","volume":"9","author":"YS Kim","year":"2020","unstructured":"Kim YS, Choi J, Yoon BE. Neuron-glia interactions in neurodevelopmental disorders. Cells. 2020;9:2176.","journal-title":"Cells"},{"key":"3787_CR56","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1007\/s12264-018-0246-2","volume":"34","author":"Q Chang","year":"2018","unstructured":"Chang Q, Yang H, Wang M, et al. Role of microtubule-associated protein in autism spectrum disorder. Neurosci Bull. 2018;34:1119\u201326.","journal-title":"Neurosci Bull"},{"key":"3787_CR57","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1002\/ajmg.a.37506","volume":"170A","author":"J DeMari","year":"2016","unstructured":"DeMari J, Mroske C, Tang S, et al. CLTC as a clinically novel gene associated with multiple malformations and developmental delay. Am J Med Genet A. 2016;170A:958\u201366.","journal-title":"Am J Med Genet A"},{"key":"3787_CR58","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1038\/s41436-019-0703-y","volume":"22","author":"MJ Nabais S\u00e1","year":"2020","unstructured":"Nabais S\u00e1 MJ, Venselaar H, Wiel L, et al. De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy. Genet Med. 2020;22:797\u2013802.","journal-title":"Genet Med"},{"key":"3787_CR59","doi-asserted-by":"publisher","first-page":"3503","DOI":"10.1007\/s00018-020-03721-6","volume":"78","author":"E Castroflorio","year":"2021","unstructured":"Castroflorio E, den Hoed J, Svistunova D, et al. The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour. Cell Mol Life Sci. 2021;78:3503\u201324.","journal-title":"Cell Mol Life Sci"},{"key":"3787_CR60","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1038\/s41467-021-22389-5","volume":"12","author":"K Aoto","year":"2021","unstructured":"Aoto K, Kato M, Akita T, et al. ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H(+)-ATPases is essential for brain development in humans and mice. Nat Commun. 2021;12:2107.","journal-title":"Nat Commun"},{"key":"3787_CR61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ymgme.2006.08.006","volume":"90","author":"WB Rizzo","year":"2007","unstructured":"Rizzo WB. Sj\u00f6gren-larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab. 2007;90:1\u20139.","journal-title":"Mol Genet Metab"},{"key":"3787_CR62","doi-asserted-by":"publisher","first-page":"3089","DOI":"10.1007\/s12035-020-01935-0","volume":"57","author":"B Toczylowska","year":"2020","unstructured":"Toczylowska B, Zieminska E, Senator P, et al. Hippocampal metabolite profiles in two rat models of autism: NMR-based metabolomics studies. Mol Neurobiol. 2020;57:3089\u2013105.","journal-title":"Mol Neurobiol"},{"key":"3787_CR63","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jocn.2018.05.001","volume":"54","author":"C Li","year":"2018","unstructured":"Li C, Shen K, Chu L, et al. Decreased levels of urinary free amino acids in children with autism spectrum disorder. J Clin Neurosci. 2018;54:45\u20139.","journal-title":"J Clin Neurosci"},{"key":"3787_CR64","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.ymgme.2016.10.009","volume":"119","author":"P Witters","year":"2016","unstructured":"Witters P, Debbold E, Crivelly K, et al. Autism in patients with propionic acidemia. Mol Genet Metab. 2016;119:317\u201321.","journal-title":"Mol Genet Metab"},{"key":"3787_CR65","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/0955-0674(94)90119-8","volume":"6","author":"N Hirokawa","year":"1994","unstructured":"Hirokawa N. Microtubule organization and dynamics dependent on microtubule-associated proteins. Curr Opin Cell Biol. 1994;6:74\u201381.","journal-title":"Curr Opin Cell Biol"},{"key":"3787_CR66","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1083\/jcb.150.5.989","volume":"150","author":"Y Takei","year":"2000","unstructured":"Takei Y, Teng J, Harada A, et al. Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes. J Cell Biol. 2000;150:989\u20131000.","journal-title":"J Cell Biol"},{"key":"3787_CR67","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.neuron.2020.01.038","volume":"106","author":"C Tai","year":"2020","unstructured":"Tai C, Chang CW, Yu GQ, et al. Tau reduction prevents key features of autism in mouse models. Neuron. 2020;106:421-37.e11.","journal-title":"Neuron"},{"key":"3787_CR68","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1126\/science.1175862","volume":"326","author":"TD Pollard","year":"2009","unstructured":"Pollard TD, Cooper JA. Actin, a central player in cell shape and movement. Science. 2009;326:1208\u201312.","journal-title":"Science"},{"key":"3787_CR69","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E22-02-0054","author":"LJ Sundby","year":"2022","unstructured":"Sundby LJ, Southern WM, Hawbaker KM, et al. Nucleotide- and protein-dependent functions of actg1. Mol Biol Cell. 2022. https:\/\/doi.org\/10.1091\/mbc.E22-02-0054.","journal-title":"Mol Biol Cell"},{"key":"3787_CR70","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1002\/cm.20475","volume":"67","author":"BJ Perrin","year":"2010","unstructured":"Perrin BJ, Ervasti JM. The actin gene family: function follows isoform. Cytoskeleton (Hoboken). 2010;67:630\u20134.","journal-title":"Cytoskeleton (Hoboken)"},{"key":"3787_CR71","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/ejhg.2014.95","volume":"23","author":"A Verloes","year":"2015","unstructured":"Verloes A, Di Donato N, Masliah-Planchon J, et al. Baraitser-winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases. Eur J Hum Genet. 2015;23:292\u2013301.","journal-title":"Eur J Hum Genet"},{"key":"3787_CR72","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.neuron.2016.02.003","volume":"89","author":"F Saudou","year":"2016","unstructured":"Saudou F, Humbert S. The biology of huntingtin. Neuron. 2016;89:910\u201326.","journal-title":"Neuron"},{"key":"3787_CR73","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/s41582-020-0389-4","volume":"16","author":"SJ Tabrizi","year":"2020","unstructured":"Tabrizi SJ, Flower MD, Ross CA, et al. Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities. Nat Rev Neurol. 2020;16:529\u201346.","journal-title":"Nat Rev Neurol"},{"key":"3787_CR74","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/s00109-020-02018-2","volume":"99","author":"L Rojas-Charry","year":"2021","unstructured":"Rojas-Charry L, Nardi L, Methner A, et al. Abnormalities of synaptic mitochondria in autism spectrum disorder and related neurodevelopmental disorders. J Mol Med (Berl). 2021;99:161\u201378.","journal-title":"J Mol Med (Berl)"},{"key":"3787_CR75","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1021\/acschemneuro.1c00800","volume":"13","author":"J Lin","year":"2022","unstructured":"Lin J, Zhang K, Cao X, et al. iTRAQ-based proteomics analysis of rat cerebral cortex exposed to valproic acid before delivery. ACS Chem Neurosci. 2022;13:648\u201363.","journal-title":"ACS Chem Neurosci"},{"key":"3787_CR76","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1111\/j.1742-4658.2007.06236.x","volume":"275","author":"H Jiang","year":"2008","unstructured":"Jiang H, Zhang XJ. Acetylcholinesterase and apoptosis. a novel perspective for an old enzyme. FEBS J. 2008;275:612\u20137.","journal-title":"FEBS J"},{"key":"3787_CR77","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1001\/archgenpsychiatry.2011.4","volume":"68","author":"K Suzuki","year":"2011","unstructured":"Suzuki K, Sugihara G, Ouchi Y, et al. Reduced acetylcholinesterase activity in the fusiform gyrus in adults with autism spectrum disorders. Arch Gen Psychiatry. 2011;68:306\u201313.","journal-title":"Arch Gen Psychiatry"},{"key":"3787_CR78","doi-asserted-by":"publisher","first-page":"195","DOI":"10.3389\/fphys.2016.00195","volume":"7","author":"PF Kinoshita","year":"2016","unstructured":"Kinoshita PF, Leite JA, Orellana AM, et al. The influence of Na(+), K(+)-ATPase on glutamate signaling in neurodegenerative diseases and senescence. Front Physiol. 2016;7:195.","journal-title":"Front Physiol"},{"key":"3787_CR79","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1177\/1073858402238515","volume":"8","author":"OA Petroff","year":"2002","unstructured":"Petroff OA. GABA and glutamate in the human brain. Neuroscientist. 2002;8:562\u201373.","journal-title":"Neuroscientist"},{"key":"3787_CR80","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/s41583-021-00443-x","volume":"22","author":"X Tang","year":"2021","unstructured":"Tang X, Jaenisch R, Sur M. The role of GABAergic signalling in neurodevelopmental disorders. Nat Rev Neurosci. 2021;22:290\u2013307.","journal-title":"Nat Rev Neurosci"},{"key":"3787_CR81","doi-asserted-by":"publisher","first-page":"70","DOI":"10.3389\/fped.2014.00070","volume":"2","author":"G Cellot","year":"2014","unstructured":"Cellot G, Cherubini E. GABAergic signaling as therapeutic target for autism spectrum disorders. Front Pediatr. 2014;2:70.","journal-title":"Front Pediatr"},{"key":"3787_CR82","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.cell.2019.12.036","volume":"180","author":"FK Satterstrom","year":"2020","unstructured":"Satterstrom FK, Kosmicki JA, Wang J, et al. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell. 2020;180:568-584.e23.","journal-title":"Cell"},{"key":"3787_CR83","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3389\/fnbeh.2018.00182","volume":"12","author":"Q Hou","year":"2018","unstructured":"Hou Q, Wang Y, Li Y, et al. A developmental study of abnormal behaviors and altered GABAergic signaling in the VPA-treated rat model of autism. Front Behav Neurosci. 2018;12:182.","journal-title":"Front Behav Neurosci"},{"key":"3787_CR84","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s13229-020-00390-x","volume":"11","author":"X Liu","year":"2020","unstructured":"Liu X, Bautista J, Liu E, et al. Imbalance of laminar-specific excitatory and inhibitory circuits of the orbitofrontal cortex in autism. Mol Autism. 2020;11:83.","journal-title":"Mol Autism"},{"key":"3787_CR85","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/85132","volume":"4","author":"AJ Hannan","year":"2001","unstructured":"Hannan AJ, Blakemore C, Katsnelson A, et al. PLC-beta1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex. Nat Neurosci. 2001;4:282\u20138.","journal-title":"Nat Neurosci"},{"key":"3787_CR86","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1093\/cercor\/bhh141","volume":"15","author":"TL Spires","year":"2005","unstructured":"Spires TL, Moln\u00e1r Z, Kind PC, et al. Activity-dependent regulation of synapse and dendritic spine morphology in developing barrel cortex requires phospholipase C-beta1 signalling. Cereb Cortex. 2005;15:385\u201393.","journal-title":"Cereb Cortex"},{"key":"3787_CR87","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.bbi.2015.05.009","volume":"49","author":"G Chana","year":"2015","unstructured":"Chana G, Laskaris L, Pantelis C, et al. Decreased expression of mGluR5 within the dorsolateral prefrontal cortex in autism and increased microglial number in mGluR5 knockout mice: pathophysiological and neurobehavioral implications. Brain Behav Immun. 2015;49:197\u2013205.","journal-title":"Brain Behav Immun"},{"key":"3787_CR88","doi-asserted-by":"publisher","first-page":"7931","DOI":"10.1523\/JNEUROSCI.22-18-07931.2002","volume":"22","author":"KW Lee","year":"2002","unstructured":"Lee KW, Hong JH, Choi IY, et al. Impaired D2 dopamine receptor function in mice lacking type 5 adenylyl cyclase. J Neurosci. 2002;22:7931\u201340.","journal-title":"J Neurosci"},{"key":"3787_CR89","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s13041-014-0077-7","volume":"7","author":"H Kim","year":"2014","unstructured":"Kim H, Kim TK, Kim JE, et al. Adenylyl cyclase-5 in the dorsal striatum function as a molecular switch for the generation of behavioral preferences for cue-directed food choices. Mol Brain. 2014;7:77.","journal-title":"Mol Brain"},{"key":"3787_CR90","doi-asserted-by":"publisher","first-page":"7994","DOI":"10.1007\/s12035-016-0256-x","volume":"54","author":"H Kim","year":"2017","unstructured":"Kim H, Lee Y, Park JY, et al. Loss of adenylyl cyclase type-5 in the dorsal striatum produces autistic-like behaviors. Mol Neurobiol. 2017;54:7994\u20138008.","journal-title":"Mol Neurobiol"},{"key":"3787_CR91","doi-asserted-by":"publisher","first-page":"e1004580","DOI":"10.1371\/journal.pgen.1004580","volume":"10","author":"CS Leblond","year":"2014","unstructured":"Leblond CS, Nava C, Polge A, et al. Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments. PLoS Genet. 2014;10:e1004580.","journal-title":"PLoS Genet"},{"key":"3787_CR92","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/ejhg.2012.175","volume":"21","author":"L Boccuto","year":"2013","unstructured":"Boccuto L, Lauri M, Sarasua SM, et al. Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders. Eur J Hum Genet. 2013;21:310\u20136.","journal-title":"Eur J Hum Genet"},{"key":"3787_CR93","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/nrn.2016.183","volume":"18","author":"P Monteiro","year":"2017","unstructured":"Monteiro P, Feng G. SHANK proteins: roles at the synapse and in autism spectrum disorder. Nat Rev Neurosci. 2017;18:147\u201357.","journal-title":"Nat Rev Neurosci"},{"key":"3787_CR94","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1523\/JNEUROSCI.3032-07.2008","volume":"28","author":"AY Hung","year":"2008","unstructured":"Hung AY, Futai K, Sala C, et al. Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. J Neurosci. 2008;28:1697\u2013708.","journal-title":"J Neurosci"},{"key":"3787_CR95","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1111\/ejn.12877","volume":"41","author":"W Mao","year":"2015","unstructured":"Mao W, Watanabe T, Cho S, et al. Shank1 regulates excitatory synaptic transmission in mouse hippocampal parvalbumin-expressing inhibitory interneurons. Eur J Neurosci. 2015;41:1025\u201335.","journal-title":"Eur J Neurosci"},{"key":"3787_CR96","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1097\/YCO.0000000000000575","volume":"33","author":"MC Lai","year":"2020","unstructured":"Lai MC, Szatmari P. Sex and gender impacts on the behavioural presentation and recognition of autism. Curr Opin Psychiatry. 2020;33:117\u201323.","journal-title":"Curr Opin Psychiatry"},{"key":"3787_CR97","doi-asserted-by":"publisher","first-page":"100786","DOI":"10.1016\/j.yfrne.2019.100786","volume":"55","author":"C Roque","year":"2019","unstructured":"Roque C, Mendes-Oliveira J, Duarte-Chendo C, et al. The role of G protein-coupled estrogen receptor 1 on neurological disorders. Front Neuroendocrinol. 2019;55:100786.","journal-title":"Front Neuroendocrinol"},{"key":"3787_CR98","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010373","author":"WJ Hwang","year":"2020","unstructured":"Hwang WJ, Lee TY, Kim NS, et al. The role of estrogen receptors and their signaling across psychiatric disorders. Int J Mol Sci. 2020. https:\/\/doi.org\/10.3390\/ijms22010373.","journal-title":"Int J Mol Sci"},{"key":"3787_CR99","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/2040-2392-5-46","volume":"5","author":"A Crider","year":"2014","unstructured":"Crider A, Thakkar R, Ahmed AO, et al. Dysregulation of estrogen receptor beta (ER\u03b2), aromatase (CYP19A1), and ER co-activators in the middle frontal gyrus of autism spectrum disorder subjects. Mol Autism. 2014;5:46.","journal-title":"Mol Autism"},{"key":"3787_CR100","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.psychres.2017.06.008","volume":"257","author":"H Altun","year":"2017","unstructured":"Altun H, Kuruta\u015f EB, \u015eahin N, et al. Decreased levels of G protein-coupled estrogen receptor in children with autism spectrum disorders. Psychiatry Res. 2017;257:67\u201371.","journal-title":"Psychiatry Res"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-022-03787-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-022-03787-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-022-03787-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T10:04:24Z","timestamp":1670666664000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-022-03787-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,6]]},"references-count":100,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["3787"],"URL":"https:\/\/doi.org\/10.1186\/s12967-022-03787-9","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,6]]},"assertion":[{"value":"28 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The present study was approved by the Animal Ethics Committee of the Ningxia Medical University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have stated that there are no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"570"}}