Disrupted neuregulin 1-ErbB4 signaling: Consequences of prenatal morphine exposure in rat pups and molecular gateway to neurological impairment

Objective: Morphine exposure during pregnancy has detrimental effects on both the mother and her offspring, both during and after childbirth. This study aimed to investigate the impact of prenatal morphine exposure on rat pups and dams, specifically focusing on changes in Neuregulin-1 (Nrg-1)/ErbB4...

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Main Authors: Samira Khayat, Hamed Fanaei, Hamid Hafezinouri, Abdolhakim Ghanbarzehi, Abolfazl Parsi-Moud, Ilia Mirzaei
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Toxicology Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2214750024000702
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author Samira Khayat
Hamed Fanaei
Hamid Hafezinouri
Abdolhakim Ghanbarzehi
Abolfazl Parsi-Moud
Ilia Mirzaei
author_facet Samira Khayat
Hamed Fanaei
Hamid Hafezinouri
Abdolhakim Ghanbarzehi
Abolfazl Parsi-Moud
Ilia Mirzaei
author_sort Samira Khayat
collection DOAJ
description Objective: Morphine exposure during pregnancy has detrimental effects on both the mother and her offspring, both during and after childbirth. This study aimed to investigate the impact of prenatal morphine exposure on rat pups and dams, specifically focusing on changes in Neuregulin-1 (Nrg-1)/ErbB4 gene expression, inflammation, and brain-derived neurotrophic factor (BDNF) levels. Materials and methods: Twenty female rats were randomized into two experimental groups:1-Morphine Group: Dams received morphine throughout pregnancy. 2-Control Group: Dams received no interventions.At the end of gestation, blood samples were collected from the dams. Subsequently, dams and their pups underwent tissue collection from the cortical area of the brain to evaluate the following parameters: Interleukin-6 (IL-6), Interleukin-10 (IL-10), total antioxidant capacity (TAC), Malondialdehyde (MDA), and Brain-derived neurotrophic factor (BDNF).Additionally, RNA was extracted from the pup's cortical brain tissue for the assessment of gene expression levels of Neuregulin-1 (NRG-1) and ErbB-4 using quantitative real-time polymerase chain reaction (qrt-PCR). Results: The molecular investigation revealed a decrease in NRG-1 and ErbB-4 expressions in the brain cortex of offspring exposed to morphine during prenatal development. Additionally, the levels of IL-6 and IL-10 in both the serum and brain of both the mothers and their offspring in the morphine group were significantly higher compared to the control group. The morphine-exposed group also exhibited significantly lower levels of TAC and higher levels of MDA, indicating increased oxidative stress. Furthermore, the levels of BDNF in the morphine group were significantly lower compared to the control group. Conclusion: Prenatal morphine exposure in rats has detrimental effects on both the dams and their offspring. This study demonstrates that prenatal morphine exposure disrupts critical molecular pathways involved in neurodevelopment, inflammation, oxidative stress, and neurotrophic signaling. These findings suggest that prenatal morphine exposure can have long-lasting consequences for the offspring, potentially contributing to neurodevelopmental disorders and other health issues later in life.
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spelling doaj-art-c781016cddb04b2cb8d93457852f77e32024-12-19T10:54:24ZengElsevierToxicology Reports2214-75002024-12-0113101687Disrupted neuregulin 1-ErbB4 signaling: Consequences of prenatal morphine exposure in rat pups and molecular gateway to neurological impairmentSamira Khayat0Hamed Fanaei1Hamid Hafezinouri2Abdolhakim Ghanbarzehi3Abolfazl Parsi-Moud4Ilia Mirzaei5Pregnancy Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; Department of Midwifery, School of Nursing and Midwifery, Zahedan University of Medical Sciences, Zahedan, IranPregnancy Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; Department of Physiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran; Correspondence to: Pregnancy Health Research Center, Zahedan University of Medical Sciences, Persian Gulf highway, Zahedan 009816875569, Iran.Laboratory Animal Research Center, Zahedan University of Medical Sciences, Zahedan, IranDepartment of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, IranSchool of Medicine, Zahedan University of Medical Sciences, Zahedan, IranSchool of Medicine, Zahedan University of Medical Sciences, Zahedan, IranObjective: Morphine exposure during pregnancy has detrimental effects on both the mother and her offspring, both during and after childbirth. This study aimed to investigate the impact of prenatal morphine exposure on rat pups and dams, specifically focusing on changes in Neuregulin-1 (Nrg-1)/ErbB4 gene expression, inflammation, and brain-derived neurotrophic factor (BDNF) levels. Materials and methods: Twenty female rats were randomized into two experimental groups:1-Morphine Group: Dams received morphine throughout pregnancy. 2-Control Group: Dams received no interventions.At the end of gestation, blood samples were collected from the dams. Subsequently, dams and their pups underwent tissue collection from the cortical area of the brain to evaluate the following parameters: Interleukin-6 (IL-6), Interleukin-10 (IL-10), total antioxidant capacity (TAC), Malondialdehyde (MDA), and Brain-derived neurotrophic factor (BDNF).Additionally, RNA was extracted from the pup's cortical brain tissue for the assessment of gene expression levels of Neuregulin-1 (NRG-1) and ErbB-4 using quantitative real-time polymerase chain reaction (qrt-PCR). Results: The molecular investigation revealed a decrease in NRG-1 and ErbB-4 expressions in the brain cortex of offspring exposed to morphine during prenatal development. Additionally, the levels of IL-6 and IL-10 in both the serum and brain of both the mothers and their offspring in the morphine group were significantly higher compared to the control group. The morphine-exposed group also exhibited significantly lower levels of TAC and higher levels of MDA, indicating increased oxidative stress. Furthermore, the levels of BDNF in the morphine group were significantly lower compared to the control group. Conclusion: Prenatal morphine exposure in rats has detrimental effects on both the dams and their offspring. This study demonstrates that prenatal morphine exposure disrupts critical molecular pathways involved in neurodevelopment, inflammation, oxidative stress, and neurotrophic signaling. These findings suggest that prenatal morphine exposure can have long-lasting consequences for the offspring, potentially contributing to neurodevelopmental disorders and other health issues later in life.http://www.sciencedirect.com/science/article/pii/S2214750024000702MorphineNeuregulin 1ErbB4PregnancyInflammationNeurodevelopment
spellingShingle Samira Khayat
Hamed Fanaei
Hamid Hafezinouri
Abdolhakim Ghanbarzehi
Abolfazl Parsi-Moud
Ilia Mirzaei
Disrupted neuregulin 1-ErbB4 signaling: Consequences of prenatal morphine exposure in rat pups and molecular gateway to neurological impairment
Toxicology Reports
Morphine
Neuregulin 1
ErbB4
Pregnancy
Inflammation
Neurodevelopment
title Disrupted neuregulin 1-ErbB4 signaling: Consequences of prenatal morphine exposure in rat pups and molecular gateway to neurological impairment
title_full Disrupted neuregulin 1-ErbB4 signaling: Consequences of prenatal morphine exposure in rat pups and molecular gateway to neurological impairment
title_fullStr Disrupted neuregulin 1-ErbB4 signaling: Consequences of prenatal morphine exposure in rat pups and molecular gateway to neurological impairment
title_full_unstemmed Disrupted neuregulin 1-ErbB4 signaling: Consequences of prenatal morphine exposure in rat pups and molecular gateway to neurological impairment
title_short Disrupted neuregulin 1-ErbB4 signaling: Consequences of prenatal morphine exposure in rat pups and molecular gateway to neurological impairment
title_sort disrupted neuregulin 1 erbb4 signaling consequences of prenatal morphine exposure in rat pups and molecular gateway to neurological impairment
topic Morphine
Neuregulin 1
ErbB4
Pregnancy
Inflammation
Neurodevelopment
url http://www.sciencedirect.com/science/article/pii/S2214750024000702
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