Oxidative Stress Impact on the Transcriptome of Differentiating Neuroblastoma Cells: Implication for Psychiatric Disorders

Khavari, Behnaz; Mahmoudi, Ebrahim; Geaghan, Michael P; Cairns, Murray J.

doi:10.3390/ijms21239182

Cited by 3 publications

(2 citation statements)

References 101 publications

(109 reference statements)

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“…Пусковым механизмом токсического действия различных стрессоров на генеративную функцию является развитие гипоксии с последующим повреждением центральной нервной системы и других органов, в основе чего лежит нарушение метаболических процессов или острый гипоксический шок [23,24]. При этом мозг является наиболее восприимчивым к недостатку кислорода.…”

Section: Discussionunclassified

Long-term consequences of acute toxic prenatal hypoxia induced by sodium nitrite in rat experiments

Savateeva-Lyubimova,

Sivak,

Aleksandrov

et al. 2023

Урал. мед. журнал

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Introduction. Gestational hypoxia plays an important role in fetal development, as it causes the development of oxidative stress and delayed psychomotor development. The aim of the study was to evaluate the prenatal effect of sodium nitrite on indices characterizing orienting and exploratory activity, mental activity and the degree of hypoxia in rat offspring. Materials and methods. Acute hypoxia was modeled by administration of sodium nitrite at a dose of 30 mg/kg intramuscularly to five pregnant rats during 16–19 days of gestation. Five females constituted a control group. In 50 born rats, orientation and exploration activity, cognitive functions, intensity of lipid peroxidation and glycolysis were studied. Results. The offspring of females that underwent acute hypoxia significantly lagged behind in the positive dynamics of body weight gain compared to control individuals. Thirty-day-old rats showed a pronounced disorder of the structure of behavioral pattern, learning process and long-term memory, increased content of diene conjugates, malonic dialdehyde and the level of lactate dehydrogenase activity in blood. Discussion. It was found that offspring whose mothers suffered acute hypoxia of toxic genesis developed pronounced behavioral disorders of psychomotor agitation and cognitive dysfunction characterized by decreased learning ability and impaired long-term memory. The content of primary and secondary products of lipid peroxidation and lactate dehydrogenase was increased in rats. The development of cellular oxidative stress under conditions of intrauterine hypoxia leads to oxygen deficiency in the fetus and a switch from tissue respiration to glycolysis, which underlies CNS damage. Conclusion. It was shown that sodium nitrite administration during the period from the 16th to the 19th day of gestation caused hyperactivity, depressed emotional status, and decreased orienting and exploratory activity and the ability to learn and retain a memory trace in rat offspring. Increased levels of diene conjugates and malonic dialdehyde, lactate dehydrogenase activity were observed in rats.

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Section: Discussionunclassified

Long-term consequences of acute toxic prenatal hypoxia induced by sodium nitrite in rat experiments

Savateeva-Lyubimova,

Sivak,

Aleksandrov

et al. 2023

Урал. мед. журнал

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“…To test this hypothesis, Ref. [1] used the most widely accepted in vitro model for neurodevelopmental and neuropsychiatric studies, the SH-SY5Y neuroblastoma cell line. The authors induced the differentiation of neuroblasts in the presence of oxidative stress and examined gene expression in mature neuronal cells.…”

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confidence: 99%

Molecular Insights in Psychiatry

Traina

Tuszyński

Cocchi

2022

IJMS

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microRNA and the Post-Transcriptional Response to Oxidative Stress during Neuronal Differentiation: Implications for Neurodevelopmental and Psychiatric Disorders

Khavari,

Barnett,

Mahmoudi

et al. 2024

Life

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Oxidative stress is one of the most important environmental exposures associated with psychiatric disorders, but the underlying molecular mechanisms remain to be elucidated. In a previous study, we observed a substantial alteration of the gene expression landscape in neuron-like cells that were differentiated from SH-SY5Y cells after or during exposure to oxidative stress, with a subset of dysregulated genes being enriched for neurodevelopmental processes. To further explore the regulatory mechanisms that might account for such profound perturbations, we have now applied small RNA-sequencing to investigate changes in the expression of miRNAs. These molecules are known to play crucial roles in brain development and response to stress through their capacity to suppress gene expression and influence complex biological networks. Through these analyses, we observed more than a hundred differentially expressed miRNAs, including 80 previously reported to be dysregulated in psychiatric disorders. The seven most influential miRNAs associated with pre-treatment exposure, including miR-138-5p, miR-96-5p, miR-34c-5p, miR-1287-5p, miR-497-5p, miR-195-5p, and miR-16-5p, supported by at least 10 negatively correlated mRNA connections, formed hubs in the interaction network with 134 genes enriched with neurobiological function, whereas in the co-treatment condition, miRNA-mRNA interaction pairs were enriched in cardiovascular and immunity-related disease ontologies. Interestingly, 12 differentially expressed miRNAs originated from the DLK1-DIO3 location, which encodes a schizophrenia-associated miRNA signature. Collectively, our findings suggest that early exposure to oxidative stress, before and during prenatal neuronal differentiation, might increase the risk of mental illnesses in adulthood by disturbing the expression of miRNAs that regulate neurodevelopmentally significant genes and networks.

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Oxidative Stress Impact on the Transcriptome of Differentiating Neuroblastoma Cells: Implication for Psychiatric Disorders

Cited by 3 publications

References 101 publications

Long-term consequences of acute toxic prenatal hypoxia induced by sodium nitrite in rat experiments

Long-term consequences of acute toxic prenatal hypoxia induced by sodium nitrite in rat experiments

Molecular Insights in Psychiatry

microRNA and the Post-Transcriptional Response to Oxidative Stress during Neuronal Differentiation: Implications for Neurodevelopmental and Psychiatric Disorders

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