دورية أكاديمية
Validation of prenatal versus postnatal valproic acid rat models of autism: A behavioral and neurobiological study.
| العنوان: | Validation of prenatal versus postnatal valproic acid rat models of autism: A behavioral and neurobiological study. |
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| المؤلفون: | Elnahas EM; Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Abuelezz SA; Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: sallyabuelezz@yahoo.com., Mohamad MI; Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Nabil MM; Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Abdelraouf SM; Department of Biochemistry, Faculty of Pharmacy, Misr International University, Cairo, Egypt., Bahaa N; Histology and Cell Biology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Hassan GA; Neuropsychiatry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Ibrahim EA; Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Ahmed AI; Anatomy and Embryology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Aboul-Fotouh S; Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. |
| المصدر: | Progress in neuro-psychopharmacology & biological psychiatry [Prog Neuropsychopharmacol Biol Psychiatry] 2021 Jun 08; Vol. 108, pp. 110185. Date of Electronic Publication: 2020 Nov 22. |
| نوع المنشور: | Comparative Study; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon Press Country of Publication: England NLM ID: 8211617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-4216 (Electronic) Linking ISSN: 02785846 NLM ISO Abbreviation: Prog Neuropsychopharmacol Biol Psychiatry Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford ; New York : Pergamon Press, c1982- |
| مواضيع طبية MeSH: | Autistic Disorder/*chemically induced , Valproic Acid/*pharmacology, Animals ; Animals, Newborn ; Apoptosis/drug effects ; Autistic Disorder/pathology ; Autistic Disorder/psychology ; Brain Chemistry/drug effects ; Cytokines/analysis ; Disease Models, Animal ; Female ; Male ; Morris Water Maze Test ; Open Field Test ; Oxidative Stress/drug effects ; Pregnancy ; Prenatal Exposure Delayed Effects/chemically induced ; Rats ; Rats, Wistar ; Reproducibility of Results ; Valproic Acid/administration & dosage |
| مستخلص: | Despite the increasing prevalence of autism spectrum disorder (ASD), there is still a deficiency in understanding its exact pathophysiology and treatment, therefore validation of translational ASD animal model is warranted. Although strong evidences support the valproic acid (VPA) model of autism, yet a controversy exists regarding the best timing of exposure whether prenatal or postnatal. Accordingly, this study was designed to compare the time dependent effects of VPA exposure as regard its ability to induce autistic like changes in male Wistar rats. In this study, two different protocols of VPA exposure (prenatal and postnatal) were compared at different levels (behavioral, neurochemical and histopathological). Results of this study revealed that both prenatal and postnatal VPA exposures induced autistic-like behaviors manifested by reduced social interaction, increased repetitive stereotyped behavior and anxiety, cognitive dysfunction, lowered sensitivity to pain, and neurodevelopmental delay. Furthermore, inflammatory cytokines and oxidative/nitrosative stress markers were elevated in prefrontal cortex and hippocampal homogenates. Likewise, histopathological and immunohistochemical assessment confirmed the neurodegenerative and the apoptotic changes in prefrontal cortex, hippocampus and cerebellum exhibited by decreased viable cells number and Nissl's granules optical density, and increased caspase-3 immunoreactivity respectively. Interestingly, ASD core symptoms and histopathological changes were significantly (P < 0.05) altered in prenatal VPA model compared to postnatal VPA model. Additionally, postnatal mortality in prenatal model (4.3%) was much lower compared to the postnatal model (22.7%). In conclusion, our study overweighs the ability of prenatal VPA model over postnatal VPA model to induce behavioral and neuropathological alterations that simulate those observed in autistic individuals with a lower postnatal animal mortality, highlighting the privilege of prenatal over postnatal VPA exposure as a translational model for understanding pathophysiology and developing novel targets for management of ASD. (Copyright © 2020 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Autism; Neuro-inflammation; Oxidative/nitrosative stress; Postnatal valproic acid; Prenatal valproic acid |
| المشرفين على المادة: | 0 (Cytokines) 614OI1Z5WI (Valproic Acid) |
| تواريخ الأحداث: | Date Created: 20201125 Date Completed: 20220124 Latest Revision: 20220124 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.pnpbp.2020.110185 |
| PMID: | 33238165 |
| قاعدة البيانات: | MEDLINE |
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