{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:25:17Z","timestamp":1793157917688,"version":"4.5.0"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The current study aimed to determine how palm date aqueous fruit extracts (AFE) affected the autistic-like behaviors brought on by valproic acid (VPA) injection, as well as any potential contributions from Sirt-1, oxidative stress, apoptosis, and autophagy. The pregnant Sprague Dawley females were treated with VPA at 12.5th gestation day and pregnant females and their offspring were treated with AFE orally at doses of 4 mg\/Kg by gastric gavage for 45 days after birth. The elevated plus-T maze, water maze, and rotarod tests were used to examine autism-like behaviors. At the end of the study, the expression of Nrf2, heme oxygenase (HO-1), Sirt-1, caspase-3 (a marker of apoptosis), LC3 (a marker of autophagy), and NF\u03baB (inflammatory cytokines) were evaluated along with the oxidative stress in brain tissues and the histological changes in the cerebellum and hippocampus. The neurobehavioral assessments significantly declined due to VPA, which also significantly increased oxidative stress in the brain tissues and significantly decreased Nrf2 and HO-1 expression. Additionally, VPA administration caused significant increase in the expression of caspase-3 in the cerebellar cortex, not in the hippocampus; LC3 and NF\u03baB in the hippocampus, not in the cerebellar cortex; and significant reduction in the expression of Sirt-1 in the hippocampus, not in the cerebellum. On the other hand, AFE treatment significantly improved the neurobehavioral changes as well as it improved significantly the oxidative stress and the expression of LC3, NF\u03baB, NrF2, HO-1, and Sirt-1 in the cerebellum and hippocampus. Conclusions: AFE administration might improve the autistic-like symptoms induced by VPA in rats via attenuation of the oxidative stress, upregulation of Nrf2 and HO-1, Sirt-1 and LC3 expression with downregulation of caspase-3, and NF\u03baB expression in the cerebellum and hippocampus.<\/jats:p>","DOI":"10.3390\/cimb45020105","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T03:09:32Z","timestamp":1676344172000},"page":"1627-1643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats"],"prefix":"10.3390","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0239-175X","authenticated-orcid":false,"given":"Abdelaziz M.","family":"Hussein","sequence":"first","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seham Ahmed","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Chemistry Department, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid Mohammed","family":"Elazab","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed F.","family":"Abouelnaga","sequence":"additional","affiliation":[{"name":"Department of Animal Husbandry and Development of Animal Wealth, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Abass","sequence":"additional","affiliation":[{"name":"Department of Surgery, Anesthesiology and Radiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6737-5788","authenticated-orcid":false,"given":"Ahmed A. H.","family":"Mosa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Delta University for Science and Technology, Gamasa 11152, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mennatullah A. M.","family":"Hussein","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0011-7837","authenticated-orcid":false,"given":"Mohamed E. G.","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy III, University of Ulm, 89075 Ulm, Germany"},{"name":"Department of Psychiatry, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.arcped.2018.06.008","article-title":"Clinical characteristics and problems diagnosing autism spectrum disorder in girls","volume":"25","author":"Young","year":"2018","journal-title":"Arch. 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