Therapeutic effect of perinatal exogenous melatonin on behavioral and histopathological changes and antioxidative enzymes in neonate mouse model of cortical malformation

Azizi, Maryam; Pasbakhsh, Parichehr; Nadji, Seyed Alireza; Pourabdollah, Mihan; Mokhtari, Tahmineh; Sadr, Makan; Omidi, Negar; Kashani, Iraj Ragerdi; Zendehdel, Adib

doi:10.1016/j.ijdevneu.2018.03.008

Cited by 13 publications

(12 citation statements)

References 33 publications

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“…Melatonin increased enzymatic expression of MnSOD and CAT. This has been previously described in neonatal pulmonary circulation [ 26 , 39 ], brain [ 55 ], and cultured cardiomyocytes [ 56 ]. Therefore, this study describes a further antioxidant regulation exerted by melatonin in neonatal hearts.…”

Section: Discussionmentioning

confidence: 75%

Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia

et al. 2021

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Pulmonary arterial hypertension of newborns (PAHN) constitutes a critical condition involving both severe cardiac remodeling and right ventricle dysfunction. One main cause of this condition is perinatal hypoxia and oxidative stress. Thus, it is a public health concern for populations living above 2500 m and in cases of intrauterine chronic hypoxia in lowlands. Still, pulmonary and cardiac impairments in PAHN lack effective treatments. Previously we have shown the beneficial effects of neonatal melatonin treatment on pulmonary circulation. However, the cardiac effects of this treatment are unknown. In this study, we assessed whether melatonin improves cardiac function and modulates right ventricle (RV) oxidative stress. Ten lambs were gestated, born, and raised at 3600 m. Lambs were divided in two groups. One received daily vehicle as control, and another received daily melatonin (1 mg·kg−1·d−1) for 21 days. Daily cardiovascular measurements were recorded and, at 29 days old, cardiac tissue was collected. Melatonin decreased pulmonary arterial pressure at the end of the experimental period. In addition, melatonin enhanced manganese superoxide dismutase and catalase (CAT) expression, while increasing CAT activity in RV. This was associated with a decrease in superoxide anion generation at the mitochondria and NADPH oxidases in RV. Finally, these effects were associated with a marked decrease of oxidative stress markers in RV. These findings support the cardioprotective effects of an oral administration of melatonin in newborns that suffer from developmental chronic hypoxia.

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Section: Discussionmentioning

confidence: 75%

Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia

et al. 2021

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“…Oxidative DNA damage (i.e., 8-oxoG) has also been observed in the brain of rodents following early-life exposure to MAM ( Steullet et al, 2017 ); this type of DNA damage is also repaired by TLS, which results in the correct insertion of a C opposite the 8-oxoG ( Markkanen et al, 2012 ). These studies demonstrate that MAM indirectly induces oxidative DNA damage in neural tissues through a transition metal-catalyzed mechanism (see Kuhnlein, 1980 ) or by reducing antioxidant enzymes ( Azizi et al, 2018 ).…”

Section: Genomic Instability and Cycad Toxinsmentioning

confidence: 95%

“…MAM is widely known as a potent genotoxin that induces alkyl and oxidative DNA lesions ( O 6 -mG, N7-mG, 8-oxoG) in many murine organs, including the brain ( Inagake et al, 1995 ; Sohn et al, 2001 ; Kisby et al, 2011 ; Álvarez-González et al, 2015 ; Steullet et al, 2017 ). The oxidative DNA lesions (8-oxoG) observed in the brain of adolescent rats in the MAM GD-17 rat model most likely occurs via hydroxyradicals formed during autooxidation in the presence of metals such as iron (see Kuhnlein, 1980 ) or by inhibiting antioxidant enzymes ( Azizi et al, 2018 ). While both DNA lesions occur in neurodevelopmental disorders and neurodegenerative diseases, interest focuses on O 6 -mG and 8-oxoG DNA lesions because they are pro-mutagenic for cycling cells and appear to be pro-cytotoxic in non-cycling cells, notably neurons ( Larsen et al, 2006 ; Spencer et al, 2012 ).…”

Section: Genomic Instability and Cycad Toxinsmentioning

confidence: 99%

Genotoxic Damage During Brain Development Presages Prototypical Neurodegenerative Disease

Kisby

Spencer

2021

Front. Neurosci.

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Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex (ALS/PDC) is a disappearing prototypical neurodegenerative disorder (tau-dominated polyproteinopathy) linked with prior exposure to phytogenotoxins in cycad seed used for medicine and/or food. The principal cycad genotoxin, methylazoxymethanol (MAM), forms reactive carbon-centered ions that alkylate nucleic acids in fetal rodent brain and, depending on the timing of systemic administration, induces persistent developmental abnormalities of the cortex, hippocampus, cerebellum, and retina. Whereas administration of MAM prenatally or postnatally can produce animal models of epilepsy, schizophrenia or ataxia, administration to adult animals produces little effect on brain structure or function. The neurotoxic effects of MAM administered to rats during cortical brain development (specifically, gestation day 17) are used to model the histological, neurophysiological and behavioral deficits of human schizophrenia, a condition that may precede or follow clinical onset of motor neuron disease in subjects with sporadic ALS and ALS/PDC. While studies of migrants to and from communities impacted by ALS/PDC indicate the degenerative brain disorder may be acquired in juvenile and adult life, a proportion of indigenous cases shows neurodevelopmental aberrations in the cerebellum and retina consistent with MAM exposure in utero. MAM induces specific patterns of DNA damage and repair that associate with increased tau expression in primary rat neuronal cultures and with brain transcriptional changes that parallel those associated with human ALS and Alzheimer’s disease. We examine MAM in relation to neurodevelopment, epigenetic modification, DNA damage/replicative stress, genomic instability, somatic mutation, cell-cycle reentry and cellular senescence. Since the majority of neurodegenerative disease lacks a solely inherited genetic basis, research is needed to explore the hypothesis that early-life exposure to genotoxic agents may trigger or promote molecular events that culminate in neurodegeneration.

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“…MAM induces N7-mG and O 6 -mG DNA lesions in rodent colon, kidney, liver, and brain, ,, while in rat neuronal cultures, the azoxy compound increased DNA lesions and reduced DNA repair (apurinic/apyrimidinic endonuclease levels) coincident with increased expression of the mRNA for tau, a microtubule-associated protein that in the hyperphosphorylated form is found in multiple neurodegenerative diseases . In addition to alkyl lesions, systemic treatment of rodents with MAM produces the promutagenic oxidative DNA lesion 8-oxoguanine (8-oxoG) in many organs, including the brain. ,− Guanine oxidation probably results from the formation of hydroxy radicals or via the inhibition of antioxidant enzymes. , Additionally, several hydrazides and acyl hydrazones are potent and selective inhibitors of 8-oxoG DNA glycosylase-1 (OGG1), which functions in the DNA base excision repair pathway to remove 8-oxoG DNA lesions. − 1,2-DMH-induced oxidative stress is an early event in liver carcinogenesis that causes the downregulation of antioxidant enzymes and OGG1 Mutm-1 homologue-1 gene expression . MAM perturbs neuronal development, − induces neuronal apoptosis, − and triggers late-onset neurobehavioral changes in rodents after in utero treatment with the genotoxin. − DNA damage is the proposed mechanism by which MAM induces neuronal loss in the developing , and aging rodent brain.…”

Section: Molecular Actions Of Hydrazine-related Compoundsmentioning

confidence: 99%

Role of Hydrazine-Related Chemicals in Cancer and Neurodegenerative Disease

Spencer

Kisby

2021

Chem. Res. Toxicol.

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Hydrazine-related chemicals (HRCs) with carcinogenic and neurotoxic potential are found in certain mushrooms and plants used for food and in products employed in various industries, including aerospace. Their propensity to induce DNA damage (mostly O 6-, N7- and 8-oxo-guanine lesions) resulting in multiple downstream effects is linked with both cancer and neurological disease. For cycling cells, unrepaired DNA damage leads to mutation and uncontrolled mitosis. By contrast, postmitotic neurons attempt to re-enter the cell cycle but undergo apoptosis or nonapoptotic cell death. Biomarkers of exposure to HRCs can be used to explore whether these substances are risk factors for sporadic amyotrophic laterals sclerosis and other noninherited neurodegenerative diseases, which is the focus of this paper.

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Therapeutic effect of perinatal exogenous melatonin on behavioral and histopathological changes and antioxidative enzymes in neonate mouse model of cortical malformation

Cited by 13 publications

References 33 publications

Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia

Melatonin Reduces Oxidative Stress in the Right Ventricle of Newborn Sheep Gestated under Chronic Hypoxia

Genotoxic Damage During Brain Development Presages Prototypical Neurodegenerative Disease

Role of Hydrazine-Related Chemicals in Cancer and Neurodegenerative Disease

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