{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T23:18:52Z","timestamp":1781824732021,"version":"3.54.5"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Autism is complex and multifactorial, and is one of the fastest growing neurodevelopmental disorders. Canagliflozin (Cana) is an antidiabetic drug that exhibits neuroprotective properties in various neurodegenerative syndromes. This study investigated the possible protective effect of Cana against the valproic acid (VPA)-induced model of autism. VPA was injected subcutaneously (SC) into rat pups at a dose of 300\u00a0mg\/kg, twice daily on postnatal day-2 (PD-2) and PD-3, and once on PD-4 to induce an autism-like syndrome. Graded doses of Cana were administered (5\u00a0mg\/kg, 7.5\u00a0mg\/kg, and 10\u00a0mg\/kg, P.O.) starting from the first day of VPA injections and continued for 21\u00a0days. At the end of the experiment, behavioral tests and histopathological alterations were assessed. In addition, the gene expression of peroxisome proliferator-activated receptor \u03b3 (PPAR \u03b3), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase (PDK), cellular myeloctomatosis (c-Myc) with protein expression of glucose transporter-1 (GLUT-1), phosphatase and tensin homolog (PTEN), and level of acetylcholine (ACh) were determined. Treatment with Cana significantly counteracted histopathological changes in the cerebellum tissues of the brain induced by VPA. Cana (5\u00a0mg\/kg, 7.5\u00a0mg\/kg, and 10\u00a0mg\/kg) improved sociability and social preference, enhanced stereotypic behaviors, and decreased hyperlocomotion activity, in addition to its significant effect on the canonical Wnt\/\u03b2-catenin pathway <jats:italic>via<\/jats:italic> the downregulation of gene expression of LDHA (22%, 64%, and 73% in cerebellum tissues with 51%, 60%, and 75% in cerebrum tissues), PDK (27%, 50%, and 67% in cerebellum tissues with 34%, 66%, and 77% in cerebrum tissues), c-Myc (35%, 44%, and 72% in cerebellum tissues with 19%, 58%, and 79% in cerebrum tissues), protein expression of GLUT-1 (32%, 48%, and 49% in cerebellum tissues with 30%, 50%, and 54% in cerebrum tissues), and elevating gene expression of PPAR-\u03b3 (2, 3, and 4 folds in cerebellum tissues with 1.5, 3, and 9 folds in cerebrum tissues), protein expression of PTEN (2, 5, and 6 folds in cerebellum tissues with 6, 6, and 10 folds in cerebrum tissues), and increasing the ACh levels (4, 5, and 7 folds) in brain tissues. The current study confirmed the ameliorating effect of Cana against neurochemical and behavioral alterations in the VPA-induced model of autism in rats.<\/jats:p>","DOI":"10.3389\/fphar.2023.1113966","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T05:08:06Z","timestamp":1677042486000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Canagliflozin alleviates valproic acid-induced autism in rat pups: Role of PTEN\/PDK\/PPAR-\u03b3 signaling pathways"],"prefix":"10.3389","volume":"14","author":[{"given":"Mariam A.","family":"Elgamal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina M.","family":"Khodeer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basel A.","family":"Abdel-Wahab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim Abdel Aziz","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah R.","family":"Alzahrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser M.","family":"Moustafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza A.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norhan M.","family":"El-Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3004","DOI":"10.1111\/j.1742-4658.2005.04713.x","article-title":"Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells","volume":"272","author":"Abbot","year":"2005","journal-title":"FEBS J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s00210-018-1564-7","article-title":"Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on cisplatin-induced nephrotoxicity in mice","volume":"392","author":"Abdelrahman","year":"2019","journal-title":"Naunyn Schmiedeb. Arch. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1007\/s00210-018-1521-5","article-title":"Mitigation of cisplatin-induced peripheral neuropathy by canagliflozin in rats","volume":"391","author":"Abdelsameea","year":"2018","journal-title":"Naunyn Schmiedeb. Arch. Pharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1007\/s13311-022-01183-1","article-title":"An update on psychopharmacological treatment of autism spectrum disorder","volume":"19","author":"Aishworiya","year":"2022","journal-title":"Neurotherapeutics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.4161\/cbt.11.12.15709","article-title":"Troglitazone suppresses c-Myc levels in human prostate cancer cells via a PPAR\u03b3-independent mechanism","volume":"11","author":"Akinyeke","year":"2011","journal-title":"Cancer Biol. Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/J.BBR.2015.02.041","article-title":"Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism","volume":"286","author":"Al-Amin","year":"2015","journal-title":"Behav. Brain Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bcp.2018.11.006","article-title":"Donepezil improves neuropathy through activation of AMPK signalling pathway in streptozotocin-induced diabetic mice","volume":"159","author":"Atef","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1590\/s1516-44462008000300016","article-title":"Cerebellum and psychiatric disorders O cerebelo e os transtornos psiqui\u00e1tricos","volume":"30","author":"Balda\u00e7ara","year":"2008","journal-title":"Braz J. Psychiatry"},{"key":"B10","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.yebeh.2017.02.026","article-title":"Effect of early postnatal exposure to valproate on neurobehavioral development and regional BDNF expression in two strains of mice","volume":"70","author":"Bath","year":"2017","journal-title":"Epilepsy Behav."},{"key":"B11","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13229-018-0222-8","article-title":"Autism spectrum disorder: Prospects for treatment using gene therapy","volume":"9","author":"Benger","year":"2018","journal-title":"Mol. Autism"},{"key":"B12","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3389\/fnbeh.2018.00317","article-title":"Social memory and social patterns alterations in the absence of striatal-enriched protein tyrosine phosphatase","volume":"12","author":"Bl\u00e1zquez","year":"2019","journal-title":"Front. Behav. Neurosci."},{"key":"B13","unstructured":"Effects of early midline cerebellar lesion on cognitive and emotional functions in the rat\n            Bob\u00e9eS.\n            MarietteE.\n            Tremblay-LeveauH.\n            CastonJ.\n          2000"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1742-2094-4-3","article-title":"Effect of pioglitazone treatment on behavioral symptoms in autistic children","volume":"4","author":"Boris","year":"2007","journal-title":"J. Neuroinflammation"},{"key":"B15","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1006\/abio.1976.9999","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13229-018-0221-9","article-title":"Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment","volume":"9","author":"Campolongo","year":"2018","journal-title":"Mol. Autism"},{"key":"B17","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/J.BBR.2016.09.003","article-title":"Downregulation of glutamatergic and GABAergic proteins in valproric acid associated social impairment during adolescence in mice","volume":"316","author":"Chau","year":"2017","journal-title":"Behav. Brain Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e0192925","DOI":"10.1371\/journal.pone.0192925","article-title":"Pathophysiological and neurobehavioral characteristics of a propionic acid-mediated autism-like rat model","volume":"13","author":"Choi","year":"2018","journal-title":"PLoS One"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1001\/JAMA.2013.2270","article-title":"Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism","volume":"309","author":"Christensen","year":"2013","journal-title":"JAMA"},{"key":"B20","doi-asserted-by":"publisher","first-page":"3490","DOI":"10.1093\/hmg\/ddu057","article-title":"Pten haploinsufficient mice show broad brain overgrowth but selective impairments in autism-relevant behavioral tests","volume":"23","author":"Clipperton-Allen","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"355","DOI":"10.3389\/fncel.2018.00355","article-title":"Neonatal oxytocin treatment ameliorates autistic-like behaviors and oxytocin deficiency in valproic acid-induced rat model of autism","volume":"12","author":"Dai","year":"2018","journal-title":"Front. Cell Neurosci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1158\/0008-5472.CAN-09-3556","article-title":"Rethinking the warburg effect with Myc micromanaging glutamine metabolism","volume":"70","author":"Dang","year":"2010","journal-title":"Cancer Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.1523\/JNEUROSCI.5488-08.2009","article-title":"Vasopressin 1b receptor knock-out impairs memory for temporal order","volume":"29","author":"DeVito","year":"2009","journal-title":"J. Neurosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"13077","DOI":"10.1038\/s41598-018-31385-7","article-title":"The histamine H3R antagonist DL77 attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism","volume":"8","author":"Eissa","year":"2018","journal-title":"Sci. Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"46","DOI":"10.2478\/enr-2019-0006","article-title":"Neuronal morphology alterations in autism and possible role of oxytocin","volume":"53","author":"el Falougy","year":"2019","journal-title":"Endocr. Regul."},{"key":"B26","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/S0278-2626(03)00281-1","article-title":"Developmental outcomes after early prefrontal cortex damage","volume":"55","author":"Eslinger","year":"2004","journal-title":"Brain Cogn."},{"key":"B27","doi-asserted-by":"publisher","first-page":"88","DOI":"10.3389\/fnbeh.2013.00088","article-title":"General developmental health in the VPA-rat model of autism","volume":"7","author":"Favre","year":"2013","journal-title":"Front. Behav. Neurosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1146\/annurev-neuro-060909-153230","article-title":"The role of the human prefrontal cortex in social cognition and moral judgment","volume":"33","author":"Forbes","year":"2010","journal-title":"Annu. Rev. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1001\/archpsyc.63.7.786","article-title":"Gray and white matter brain chemistry in young children with autism","volume":"63","author":"Friedman","year":"2006","journal-title":"Arch. Gen. Psychiatry"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1016\/j.biopsych.2010.09.031","article-title":"Validating \u03b3 oscillations and delayed auditory responses as translational biomarkers of autism","volume":"68","author":"Gandal","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"B31","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/J.PSYCHRES.2015.07.043","article-title":"A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone: Effects on aberrant behavior in children with autism","volume":"229","author":"Ghaleiha","year":"2015","journal-title":"Psychiatry Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"S25","DOI":"10.1177\/088307380401900104","article-title":"Behavioral and psychiatric adverse events associated with antiepileptic drugs commonly used in pediatric patients","volume":"19","author":"Glauser","year":"2004","journal-title":"J. Child. Neurol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"11717","DOI":"10.1073\/pnas.1120068109","article-title":"Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors","volume":"109","author":"Gurney","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B34","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/J.BBR.2016.10.004","article-title":"Human adipose-derived stem cells ameliorate repetitive behavior, social deficit and anxiety in a VPA-induced autism mouse model","volume":"317","author":"Ha","year":"2017","journal-title":"Behav. Brain Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"91","DOI":"10.21608\/ejana.2018.43506","article-title":"A study of the effect of prenatal exposure to valproic acid on the cerebellum of albino rat\u2019s offspring and the possible protective role of folic acid","volume":"41","author":"Hafez","year":"2018","journal-title":"Egypt. J. Anat."},{"key":"B36","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1385\/JMN:18:1-2:151","article-title":"Evaluation of an anxiety-related phenotype in galanin overexpressing transgenic mice","volume":"18","author":"Holmes","year":"2002","journal-title":"J. Mol. Neurosci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/s41419-019-1646-6","article-title":"Canagliflozin inhibits growth of hepatocellular carcinoma via blocking glucose-influx-induced \u03b2-catenin activation","volume":"10","author":"Hung","year":"2019","journal-title":"Cell Death Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e20193447","DOI":"10.1542\/PEDS.2019-3447","article-title":"Identification, evaluation, and management of children with autism spectrum disorder","volume":"145","author":"Hyman","year":"2020","journal-title":"Pediatrics"},{"key":"B39","unstructured":"The Wnt-catenin signaling pathway targets PPAR activity in colon cancer cells\n            JanssonE. \u00c5.\n            AreA.\n            GreiciusG.\n            KuoI.-C.\n            KellyD.\n            ArulampalamV.\n          2005"},{"key":"B40","first-page":"217","article-title":"kanner, 1943","volume":"2","author":"Kanner","year":"1943","journal-title":"Nerv. Child."},{"key":"B41","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1038\/npp.2013.274","article-title":"Acetylcholine elevation relieves cognitive rigidity and social deficiency in a mouse model of autism","volume":"39","author":"Karvat","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1007\/s11011-017-0085-2","article-title":"Novel biomarkers of metabolic dysfunction is autism spectrum disorder: Potential for biological diagnostic markers","volume":"32","author":"Khemakhem","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/J.NEUROPHARM.2016.09.014","article-title":"Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism","volume":"113","author":"Kim","year":"2017","journal-title":"Neuropharmacology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e104927","DOI":"10.1371\/journal.pone.0104927","article-title":"Subchronic treatment of donepezil rescues impaired social, hyperactive, and stereotypic behavior in valproic acid-induced animal model of autism","volume":"9","author":"Kim","year":"2014","journal-title":"PLoS One"},{"key":"B45","doi-asserted-by":"publisher","first-page":"e0197060","DOI":"10.1371\/journal.pone.0197060","article-title":"Pioglitazone abolishes autistic-like behaviors via the IL-6 pathway","volume":"13","author":"Kirsten","year":"2018","journal-title":"PLoS One"},{"key":"B46","doi-asserted-by":"publisher","first-page":"bio041327","DOI":"10.1242\/bio.041327","article-title":"Pioglitazone abolishes cognition impairments as well as BDNF and neurotensin disturbances in a rat model of autism","volume":"8","author":"Kirsten","year":"2019","journal-title":"Biol. Open"},{"key":"B47","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1055\/S-0031-1293538","article-title":"Epilepsy cases in pregnant and postpartum women: A practical approach","volume":"31","author":"Klein","year":"2011","journal-title":"Semin. Neurol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s11689-016-9176-3","article-title":"Wnt signaling networks in autism spectrum disorder and intellectual disability","volume":"8","author":"Kwan","year":"2016","journal-title":"J. Neurodev. Disord."},{"key":"B49","doi-asserted-by":"publisher","first-page":"8863256","DOI":"10.1155\/2021\/8863256","article-title":"A need for consistency in behavioral phenotyping for ASD: Analysis of the valproic acid model","volume":"2021","author":"Larner","year":"2021","journal-title":"Autism Res. Treat."},{"key":"B50","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s40169-017-0144-7","article-title":"Thermodynamics in cancers: Opposing interactions between PPAR gamma and the canonical WNT\/beta\u2010catenin pathway","volume":"6","author":"Lecarpentier","year":"2017","journal-title":"Clin. Transl. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1002\/dneu.22359","article-title":"Valproic acid stimulates proliferation of glial precursors during cortical gliogenesis in developing rat","volume":"76","author":"Lee","year":"2016","journal-title":"Dev. Neurobiol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1523\/JNEUROSCI.1896-17.2017","article-title":"Conditional deletion of hippocampal CA2\/CA3a oxytocin receptors impairs the persistence of long-term social recognition memory in mice","volume":"38","author":"Lin","year":"2018","journal-title":"J. Neurosci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s13229-018-0197-5","article-title":"Impairment of social behaviors in Arhgef10 knockout mice","volume":"9","author":"Lu","year":"2018","journal-title":"Mol. Autism"},{"key":"B54","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3389\/fnmol.2014.00027","article-title":"Deletion of PTEN produces autism-like behavioral deficits and alterations in synaptic proteins","volume":"7","author":"Lugo","year":"2014","journal-title":"Front. Mol. Neurosci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.neuroscience.2016.10.052","article-title":"Repeated prenatal exposure to valproic acid results in cerebellar hypoplasia and ataxia","volume":"340","author":"Main","year":"2017","journal-title":"Neuroscience"},{"key":"B56","unstructured":"Environmental enrichment ameliorates repetitive behaviors in a rat model of autism\n            MansouriM.\n            PouretemadH.\n            RoghaniM.\n            WegenerG.\n            ArdalanM.\n          2019"},{"key":"B57","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1111\/j.1460-9568.2009.07073.x","article-title":"Repetitive behavior and increased activity in mice with purkinje cell loss: A model for understanding the role of cerebellar pathology in autism","volume":"31","author":"Martin","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/J.EJPHAR.2004.02.041","article-title":"Glucose transporter expression in the central nervous system: Relationship to synaptic function","volume":"490","author":"McEwen","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e62189","DOI":"10.1371\/journal.pone.0062189","article-title":"The BTBR mouse model of autism spectrum disorders has learning and attentional impairments and alterations in acetylcholine and kynurenic acid in prefrontal cortex","volume":"8","author":"McTighe","year":"2013","journal-title":"PLoS One"},{"key":"B60","doi-asserted-by":"publisher","first-page":"e26077","DOI":"10.1371\/journal.pone.0026077","article-title":"mGluR5-antagonist mediated reversal of elevated stereotyped, repetitive behaviors in the VPA model of autism","volume":"6","author":"Mehta","year":"2011","journal-title":"PLoS One"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1007\/s10787-020-00724-4","article-title":"Perindopril ameliorates experimental alzheimer\u2019s disease progression: Role of amyloid \u03b2 degradation, central estrogen receptor and hyperlipidemic-lipid raft signaling","volume":"28","author":"Messiha","year":"2020","journal-title":"Inflammopharmacology"},{"key":"B62","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s00213-019-05357-2","article-title":"Improvement of autistic-like behaviors in adult rats prenatally exposed to valproic acid through early suppression of NMDA receptor function","volume":"237","author":"Mohammadi","year":"2020","journal-title":"Psychopharmacol. Berl."},{"key":"B63","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1042\/BJ20030426","article-title":"Peroxisome-proliferator-activated receptor \u03b3 suppresses Wnt\/\u03b2-catenin signalling during adipogenesis","volume":"376","author":"Moldes","year":"2003","journal-title":"Biochem. J."},{"key":"B64","doi-asserted-by":"publisher","first-page":"338","DOI":"10.9758\/cpn.2016.14.4.338","article-title":"Valproic acid exposure during early postnatal gliogenesis leads to autistic-like behaviors in rats","volume":"14","author":"Mony","year":"2016","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"214","DOI":"10.9758\/cpn.2018.16.2.214","article-title":"Early postnatal valproic acid exposure increase the protein level of astrocyte markers in frontal cortex of rat","volume":"16","author":"Mony","year":"2018","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"3206561","DOI":"10.1155\/2016\/3206561","article-title":"Autistic-like behaviors, oxidative stress status, and histopathological changes in cerebellum of valproic acid rat model of autism are improved by the combined extract of purple rice and silkworm pupae","volume":"2016","author":"Morakotsriwan","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"B67","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1159\/000453266","article-title":"Neurodevelopmental perspectives on Wnt signaling in psychiatry","volume":"2","author":"Mulligan","year":"2016","journal-title":"Mol. Neuropsychiatry"},{"key":"B68","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1159\/000341786","article-title":"Effects of rat prenatal exposure to valproic acid on behaviour and neuro-anatomy","volume":"34","author":"Mychasiuk","year":"2012","journal-title":"Dev. Neurosci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/J.EJPHAR.2016.11.028","article-title":"Canagliflozin, a sodium glucose cotransporter 2 inhibitor, attenuates obesity-induced inflammation in the nodose ganglion, hypothalamus, and skeletal muscle of mice","volume":"794","author":"Naznin","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"e55261","DOI":"10.3791\/55261","article-title":"Neurodevelopmental reflex testing in neonatal rat pups","volume":"122","author":"Nguyen","year":"2017","journal-title":"JoVE J. Vis. Exp."},{"key":"B71","doi-asserted-by":"publisher","first-page":"6355","DOI":"10.1021\/jm100332n","article-title":"Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus","volume":"53","author":"Nomura","year":"2010","journal-title":"J. Med. Chem."},{"key":"B72","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/J.BRAINRES.2007.06.074","article-title":"A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice","volume":"1168","author":"Ogawa","year":"2007","journal-title":"Brain Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/0091-3057(86)90552-6","article-title":"Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: A novel test of anxiety in the rat","volume":"24","author":"Pellow","year":"1986","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B74","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.cell.2011.08.040","article-title":"Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits","volume":"147","author":"Pe\u00f1agarikano","year":"2011","journal-title":"Cell"},{"key":"B75","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/J.EJMG.2012.11.003","article-title":"Deletion 1q43 encompassing only CHRM3 in a patient with autistic disorder","volume":"56","author":"Petersen","year":"2013","journal-title":"Eur. J. Med. Genet."},{"key":"B76","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.neuron.2012.08.036","article-title":"Acetylcholine as a neuromodulator: Cholinergic signaling shapes nervous system function and behavior","volume":"76","author":"Picciotto","year":"2012","journal-title":"Neuron"},{"key":"B77","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/S0006-3223(00)01008-8","article-title":"Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism","volume":"49","author":"Pierce","year":"2001","journal-title":"Biol. Psychiatry"},{"key":"B78","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/J.PNPBP.2015.01.003","article-title":"A single dose of PPAR\u03b3 agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats","volume":"59","author":"Pilipovi\u0107","year":"2015","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B79","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1080\/15569543.2019.1680563","article-title":"Does caffeine therapy improve cognitive impairments in valproic acid rat model of autism?","volume":"40","author":"Rajizadeh","year":"2021","journal-title":"Toxin Rev."},{"key":"B80","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1017\/S0012162205001076","article-title":"Characteristics of fetal anticonvulsant syndrome associated autistic disorder","volume":"47","author":"Rasalam","year":"2005","journal-title":"Dev. Med. Child. Neurol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S0079-6603(01)70013-X","article-title":"Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms","volume":"70","author":"Roche","year":"2001","journal-title":"Prog. Nucleic Acid. Res. Mol. Biol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/J.NEUROSCIENCE.2010.06.069","article-title":"Behavioral and molecular changes in the mouse in response to prenatal exposure to the anti-epileptic drug valproic acid","volume":"170","author":"Roullet","year":"2010","journal-title":"Neuroscience"},{"key":"B83","doi-asserted-by":"publisher","first-page":"493","DOI":"10.4196\/kjpp.2018.22.5.493","article-title":"The combination of canagliflozin and omega-3 fatty acid ameliorates insulin resistance and cardiac biomarkers via modulation of inflammatory cytokines in type 2 diabetic rats","volume":"22","author":"Safhi","year":"2018","journal-title":"Korean J. Physiology Pharmacol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.1038\/s41598-019-39014-7","article-title":"Consequences of prenatal exposure to valproic acid in the socially monogamous prairie voles","volume":"9","author":"Sailer","year":"2019","journal-title":"Sci. Rep."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.3390\/PH15081012","article-title":"Neuroprotective effect of morin hydrate against attention-deficit\/hyperactivity disorder (ADHD) induced by MSG and\/or protein malnutrition in rat pups: Effect on oxidative\/monoamines\/inflammatory balance and apoptosis","volume":"15","author":"Salem","year":"2022","journal-title":"Pharm. (Basel)"},{"key":"B86","first-page":"164","article-title":"The effect of gallic acid on histopathologic evaluation of cerebellum in valproic acid-induced autism animal models","volume":"5","author":"Samimi","year":"2016","journal-title":"Int. J. Med. Res. Health Sci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/nature11015","article-title":"Autistic-like behaviours and hyperactivity in mice lacking ProSAP1\/Shank2","volume":"486","author":"Schmeisser","year":"2012","journal-title":"Nature"},{"key":"B88","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1038\/sj.npp.1300634","article-title":"Deficient social and play behavior in juvenile and adult rats after neonatal cortical lesion: Effects of chronic pubertal cannabinoid treatment","volume":"30","author":"Schneider","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"B89","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/sj.npp.1300518","article-title":"Behavioral alterations in rats prenatally exposed to valproic acid: Animal model of autism","volume":"30","author":"Schneider","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"B90","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/J.PSYNEUEN.2008.02.011","article-title":"Gender-specific behavioral and immunological alterations in an animal model of autism induced by prenatal exposure to valproic acid","volume":"33","author":"Schneider","year":"2008","journal-title":"Psychoneuroendocrinology"},{"key":"B91","doi-asserted-by":"publisher","first-page":"201","DOI":"10.5603\/FM.a2017.0100","article-title":"Effect of valproic acid administration during pregnancy on postnatal development of cerebellar cortex and the possible protective role of folic acid","volume":"77","author":"Shona","year":"2018","journal-title":"Folia Morphol. Pol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1001\/archpsyc.59.11.1027","article-title":"Increased amygdala activation to angry and contemptuous faces in generalized social phobia","volume":"59","author":"Stein","year":"2002","journal-title":"Arch. Gen. Psychiatry"},{"key":"B93","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/J.EPLEPSYRES.2011.09.008","article-title":"Antiepileptic drug combinations--have newer agents altered clinical outcomes?","volume":"98","author":"Stephen","year":"2012","journal-title":"Epilepsy Res."},{"key":"B94","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1080\/08039480410005774","article-title":"Why do some individuals develop social phobia? A review with emphasis on the neurobiological influences","volume":"58","author":"Tillfors","year":"2004","journal-title":"Nord. J. Psychiatry"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1016\/J.JOCN.2012.05.003","article-title":"Dose issues in antiepileptic therapy","volume":"19","author":"Vajda","year":"2012","journal-title":"J. Clin. Neurosci."},{"key":"B96","unstructured":"Interactions between TGF-\u03b21, canonical WNT\/\u03b2-catenin pathway and PPAR \u03b3 in radiation-induced fibrosis\n            Vall\u00e9eA.\n            LecarpentierY.\n            GuillevinR.\n            Vall\u00e9eJ.-N.\n          2017"},{"key":"B97","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13041-017-0343-6","article-title":"Warburg effect hypothesis in autism Spectrum disorders","volume":"11","author":"Vall\u00e9e","year":"2018","journal-title":"Mol. Brain"},{"key":"B98","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1007\/s10803-006-0117-y","article-title":"A new neurobehavioral model of autism in mice: Pre- and postnatal exposure to sodium valproate","volume":"36","author":"Wagner","year":"2006","journal-title":"J. Autism Dev. Disord."},{"key":"B99","doi-asserted-by":"publisher","first-page":"379","DOI":"10.3390\/ph13110379","article-title":"Perspective of sglt2 inhibition in treatment of conditions connected to neuronal loss: Focus on alzheimer\u2019s disease and ischemia-related brain injury","volume":"13","author":"Wici\u0144ski","year":"2020","journal-title":"Pharmaceuticals"},{"key":"B100","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/J.LFS.2017.01.012","article-title":"Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism","volume":"173","author":"Wu","year":"2017","journal-title":"Life Sci."},{"key":"B101","doi-asserted-by":"publisher","first-page":"e0153298","DOI":"10.1371\/journal.pone.0153298","article-title":"Early behavioral abnormalities and perinatal alterations of PTEN\/AKT pathway in valproic acid autism model mice","volume":"11","author":"Yang","year":"2016","journal-title":"PLoS One"},{"key":"B102","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.cell.2012.07.018","article-title":"PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis","volume":"150","author":"Yang","year":"2012","journal-title":"Cell"},{"key":"B106","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/J.BRAINRES.2010.10.032","article-title":"Interruption of \u03b2-catenin suppresses the EGFR pathway by blocking multiple oncogenic targets in human glioma cells","volume":"1366","author":"Yue","year":"2010","journal-title":"Brain Res."},{"key":"B103","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1743-7075-11-10","article-title":"The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility","volume":"11","author":"Zhang","year":"2014","journal-title":"Nutr. Metab. (Lond)"},{"key":"B104","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1007\/s11064-012-0724-2","article-title":"Downregulating the canonical Wnt\/\u03b2-catenin signaling pathway attenuates the susceptibility to autism-like phenotypes by decreasing oxidative stress","volume":"37","author":"Zhang","year":"2012","journal-title":"Neurochem. Res."},{"key":"B105","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/J.CONB.2012.05.004","article-title":"PTEN signaling in autism spectrum disorders","volume":"22","author":"Zhou","year":"2012","journal-title":"Curr. Opin. Neurobiol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1113966\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T05:08:10Z","timestamp":1677042490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1113966\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,22]]},"references-count":105,"alternative-id":["10.3389\/fphar.2023.1113966"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1113966","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,22]]},"article-number":"1113966"}}