Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats

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 t...

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Main Authors: Abdelaziz M. Hussein, Seham Ahmed Mahmoud, Khalid Mohammed Elazab, Ahmed F. Abouelnaga, Marwa Abass, Ahmed A. H. Mosa, Mennatullah A. M. Hussein, Mohamed E. G. Elsayed
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Current Issues in Molecular Biology
Subjects:
Online Access:https://www.mdpi.com/1467-3045/45/2/105
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author Abdelaziz M. Hussein
Seham Ahmed Mahmoud
Khalid Mohammed Elazab
Ahmed F. Abouelnaga
Marwa Abass
Ahmed A. H. Mosa
Mennatullah A. M. Hussein
Mohamed E. G. Elsayed
author_facet Abdelaziz M. Hussein
Seham Ahmed Mahmoud
Khalid Mohammed Elazab
Ahmed F. Abouelnaga
Marwa Abass
Ahmed A. H. Mosa
Mennatullah A. M. Hussein
Mohamed E. G. Elsayed
author_sort Abdelaziz M. Hussein
collection DOAJ
description 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 NFκB (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 NFκB 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, NFκB, 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 NFκB expression in the cerebellum and hippocampus.
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spelling doaj.art-45b1832db3ce454eb46611e50e861a802023-11-16T19:51:11ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-02-014521627164310.3390/cimb45020105Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in RatsAbdelaziz M. Hussein0Seham Ahmed Mahmoud1Khalid Mohammed Elazab2Ahmed F. Abouelnaga3Marwa Abass4Ahmed A. H. Mosa5Mennatullah A. M. Hussein6Mohamed E. G. Elsayed7Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptChemistry Department, Zagazig University, Zagazig 44519, EgyptDepartment of Biology, Faculty of Science, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Animal Husbandry and Development of Animal Wealth, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Surgery, Anesthesiology and Radiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Neurology, Faculty of Medicine, Delta University for Science and Technology, Gamasa 11152, EgyptFaculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Psychiatry and Psychotherapy III, University of Ulm, 89075 Ulm, GermanyThe 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 NFκB (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 NFκB 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, NFκB, 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 NFκB expression in the cerebellum and hippocampus.https://www.mdpi.com/1467-3045/45/2/105palm date extractsVPAautismSirt-1oxidative stressNrf2
spellingShingle Abdelaziz M. Hussein
Seham Ahmed Mahmoud
Khalid Mohammed Elazab
Ahmed F. Abouelnaga
Marwa Abass
Ahmed A. H. Mosa
Mennatullah A. M. Hussein
Mohamed E. G. Elsayed
Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats
Current Issues in Molecular Biology
palm date extracts
VPA
autism
Sirt-1
oxidative stress
Nrf2
title Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats
title_full Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats
title_fullStr Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats
title_full_unstemmed Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats
title_short Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats
title_sort possible mechanisms of the neuroprotective actions of date palm fruits aqueous extracts against valproic acid induced autism in rats
topic palm date extracts
VPA
autism
Sirt-1
oxidative stress
Nrf2
url https://www.mdpi.com/1467-3045/45/2/105
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