{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T22:21:32Z","timestamp":1786486892259,"version":"build-2736575974"},"reference-count":68,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Autism Research"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology and phenotypes. Phosphodiesterase\u20101 (PDE1) inhibitors are known to provide benefits in various brain conditions manifesting similar behavioral phenotypes. The pharmacological consequences of vinpocetine administration a PDE1 inhibitor in prenatal\u2010valproic acid (pre\u2010VPA) induced ASD related behavioral phenotypes (social behavior deficits, repetitive behavior, anxiety, hyperlocomotion, and nociception) was assessed. Also, effects on important biochemical markers of neuronal function (DCX\u2010neurogenesis, BDNF\u2010neuronal survival, synapsin\u2010IIa\u2010synaptic transmission, pCREB\u2010neuronal transcription factor), inflammation (interleukin [IL]\u20106, IL\u201010, and TNF\u2010\u03b1) and oxidative stress (thiobarbituric acid reactive substance [TBARS] and glutathione (GSH) were studied in important brain areas (frontal cortex, cerebral cortex, hippocampus, and striatum). Further, neuronal cell viability was determined in dentate gyrus using Nissl staining. Pre\u2010VPA administration resulted into impaired behavior, brain biochemistry, and neuronal cell viability. Administration of vinpocetine resulted in improvements of pre\u2010VPA impaired social behavior, repetitive behavior, anxiety, locomotion, and nociception. Also, vinpocetine resulted in a significant increase in the levels of BDNF, synapsin\u2010IIa, DCX, pCREB\/CREB, IL\u201010, and GSH along with significant decrease in TNF\u2010\u03b1, IL\u20106, TBARS, number of pyknotic and chromatolytic cells in different brain areas of pre\u2010VPA group. Finally, high association between behavioral parameters and biochemical parameters was observed upon Pearson's correlation analysis. Vinpocetine, a PDE1 inhibitor rectified important behavioral phenotypes related with ASD, possibly by improving neuronal function, brain inflammation and brain oxidative stress. Thus, PDE1 may be a possible target for further understanding ASD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Lay Summary<\/jats:title><jats:p>ASD is a brain developmental disorder with a wide array of genetic and environmental factors. Many targets have been identified till date, but a clinical treatment is still afar. The results of this study indicate that vinpocetine administration resulted in amelioration of ASD associated symptomatology in rats, prenatally exposed to VPA. Our research adds a widely expressed brain enzyme PDE1, as a possible novel pharmacological target and opens\u2010up a new line of enquiry for ASD treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/aur.2597","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T10:13:11Z","timestamp":1629454391000},"page":"2270-2286","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Vinpocetine amended prenatal valproic acid induced features of <scp>ASD<\/scp> possibly by altering markers of neuronal function, inflammation, and oxidative stress"],"prefix":"10.1002","volume":"14","author":[{"given":"Kanishk","family":"Luhach","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Amity Institute of Pharmacy Amity University  Noida Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giriraj T.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Gokaraju Rangaraju College of Pharmacy  Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay P.","family":"Singh","sequence":"additional","affiliation":[{"name":"CSIR\u2010Institute of Genomics &amp; Integrative Biology Academy of scientific and Innovative research  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3423-007X","authenticated-orcid":false,"given":"Bhupesh","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Amity Institute of Pharmacy Amity University  Noida Uttar Pradesh India"},{"name":"CNS and CVS Pharmacology Conscience Research  Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2018.04.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-018-1552-y"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.03.010"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24072"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-00997-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2009.12.017"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00030.2010"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.12.015"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0404.2002.01302.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-002-0823-4"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.01.004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.03.032"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567202612666150603130235"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-018-0256-9"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1054-09.2009"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006643"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2016.03.013"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2015.10.052"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2015.10.007"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.5625\/lar.2018.34.4.239"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2010.05.004"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.09.013"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.12965\/jer.1632638.319"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/251785"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.2.796"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173663"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18020455"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16009"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301453"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2014.02.012"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2011.00021"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14435"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2011.07606.x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.10.045"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2019.05.006"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2019.02.003"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.9758\/cpn.2016.14.4.338"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2323-8"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.22-22-09868.2002"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2011.05.024"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5949.2009.00078.x"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8363274"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.11.041"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2019.104476"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1723401"},{"key":"e_1_2_9_48_1","first-page":"53","article-title":"Valproic acid and autism Spectrum disorder: From clinical observations to animal studies","volume":"11","author":"Roux S.","year":"2018","journal-title":"Current Trends in Neurology"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2015.05.007"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0118942"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300518"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1254\/fpj.80.221"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2392-2-7"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23894"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-015-0611-9"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-016-9660-2"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0655-4"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.01.012"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4805-4"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.comppsych.2019.152122"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-03-00973.1994"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12991-016-0095-1"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.4306\/pi.2014.11.3.319"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1191\/135245899678847194"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.02.1180"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep29551"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2018.01.008"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-012-0724-2"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.11.041"}],"container-title":["Autism Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/aur.2597","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/aur.2597","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/aur.2597","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T18:56:57Z","timestamp":1692989817000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/aur.2597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,20]]},"references-count":68,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1002\/aur.2597"],"URL":"https:\/\/doi.org\/10.1002\/aur.2597","archive":["Portico"],"relation":{},"ISSN":["1939-3792","1939-3806"],"issn-type":[{"value":"1939-3792","type":"print"},{"value":"1939-3806","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,20]]},"assertion":[{"value":"2020-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}