Apelin-13 attenuates spatial memory impairment by anti-oxidative, anti-apoptosis, and anti-inflammatory mechanism against ethanol neurotoxicity in the neonatal rat hippocampus

Mohseni, Fahimeh; Garmabi, Behzad; Khaksari, Mehdi

doi:10.1016/j.npep.2021.102130

Cited by 12 publications

(3 citation statements)

References 66 publications

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“…These deficits are possibly ameliorated due to the anti-inflammatory properties of apelin. It increased the expression of antioxidant enzymes, decreased the level of apoptotic-associated proteins, and attenuated TNF-α production, as well as lipid peroxidation, resulting in a decrease in neuronal cell death [121]. The research shows apelin-13 as a promising therapeutic choice for FASD; however, further studies are needed to assess the effects of apelin on other brain regions and deficits that accompany them.…”

Section: Apelin-13mentioning

confidence: 99%

The Fetal Alcohol Spectrum Disorders—An Overview of Experimental Models, Therapeutic Strategies, and Future Research Directions

Król,

Skowron,

Skowron

et al. 2024

Children

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Since the establishment of a clear link between maternal alcohol consumption during pregnancy and certain birth defects, the research into the treatment of FASD has become increasingly sophisticated. The field has begun to explore the possibility of intervening at different levels, and animal studies have provided valuable insights into the pathophysiology of the disease, forming the basis for implementing potential therapies with increasingly precise mechanisms. The recent reports suggest that compounds that reduce the severity of neurodevelopmental deficits, including glial cell function and myelination, and/or target oxidative stress and inflammation may be effective in treating FASD. Our goal in writing this article was to analyze and synthesize current experimental therapeutic interventions for FASD, elucidating their potential mechanisms of action, translational relevance, and implications for clinical application. This review exclusively focuses on animal models and the interventions used in these models to outline the current direction of research. We conclude that given the complexity of the underlying mechanisms, a multifactorial approach combining nutritional supplementation, pharmacotherapy, and behavioral techniques tailored to the stage and severity of the disease may be a promising avenue for further research in humans.

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Section: Apelin-13mentioning

confidence: 99%

The Fetal Alcohol Spectrum Disorders—An Overview of Experimental Models, Therapeutic Strategies, and Future Research Directions

Król,

Skowron,

Skowron

et al. 2024

Children

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show abstract

“…Interestingly, these different processes are frequently interconnected and regulated by the same intracellular pathways [45]. Indeed, apelin's beneficial properties on ethanol-induced memory impairment and neuronal injury of rats are sustained by inhibitory effects on hippocampal oxidative stress, apoptosis, and neuroinflammation [140]. Specifically, the administration of apelin-13 was observed to increase antioxidant enzymes' activity and glutathione concentration, reduce lipid peroxidation and the number of active caspase-3 positive cells, and attenuate TNF-α production and glial fibrillary acidic protein (GFAP) as a neuroinflammation mediators [140].…”

Section: Oxidative Stress In the Central Nervous Systemmentioning

confidence: 99%

The Yin and Yang Effect of the Apelinergic System in Oxidative Stress

Fibbi

Marroncini

Naldi

et al. 2023

IJMS

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Apelin is an endogenous ligand for the G protein-coupled receptor APJ and has multiple biological activities in human tissues and organs, including the heart, blood vessels, adipose tissue, central nervous system, lungs, kidneys, and liver. This article reviews the crucial role of apelin in regulating oxidative stress-related processes by promoting prooxidant or antioxidant mechanisms. Following the binding of APJ to different active apelin isoforms and the interaction with several G proteins according to cell types, the apelin/APJ system is able to modulate different intracellular signaling pathways and biological functions, such as vascular tone, platelet aggregation and leukocytes adhesion, myocardial activity, ischemia/reperfusion injury, insulin resistance, inflammation, and cell proliferation and invasion. As a consequence of these multifaceted properties, the role of the apelinergic axis in the pathogenesis of degenerative and proliferative conditions (e.g., Alzheimer’s and Parkinson’s diseases, osteoporosis, and cancer) is currently investigated. In this view, the dual effect of the apelin/APJ system in the regulation of oxidative stress needs to be more extensively clarified, in order to identify new potential strategies and tools able to selectively modulate this axis according to the tissue-specific profile.

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“…Oxidative stress and in ammation are considered the major mechanisms in the pathogenesis of ethanol addiction and withdrawal (Schneider et al 2017;Mohseni et al 2021). Excessive exposure to ethanol induces overexpression of reactive oxygen species (ROS), resulting in abnormal expression of GSH, MDA and SOD (Contreras et al 2017), which is mainly conducted by the nuclear factor erythroid 2-related Factor 2 (Nrf2)-mediated antioxidative signaling pathway (Quintanilla et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Irisin attenuates ethanol-induced behavioral deficits in mice through activation of Nrf2 and inhibition of NF-κB pathways

et al. 2023

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This study aims to investigate the effect of irisin on ethanol-induced behavioral de cits and explore the underlying mechanisms. A mouse model of ethanol addiction/withdrawal was constructed through chronic ethanol administration. Depressive-like behaviors were evaluated by the tail suspension test and forced swimming test, and anxiety-like behaviors were evaluated by the marble-burying test and elevated plus maze test. The expression of Nrf2 was measured by western blotting. Levels of in ammatory mediators (NF-κB, TNF-α, IL-1β and IL-6) and oxidative stress factors (ROS, MDA, GSH and SOD) were detected by ELISA. The ethanol-induced PC12/BV2 cell injury model was used to elucidate whether the effect of irisin on ethanol-induced neurological injury was related to anti-in ammatory and antioxidant mechanisms. Ethanol-induced ethanol preference and emotional de cits were improved by chronic irisin treatment; however, these improvements were partly reversed by cotreatment with the Nrf2 inhibitor ML385. Further results implied that the improvement effect of irisin on behavioral abnormalities may be related to its anti-in ammatory and antioxidant effects. In detail, irisin inhibited ethanol-induced abnormal expression of ROS and MDA and upregulated the expression of GSH and SOD. Meanwhile, irisin treatment inhibited ethanol-induced overexpression of NF-κB, TNF-α, IL-1β and IL-6 in the hippocampus and cerebral cortex. The regulation of oxidative stress factors by irisin was reversed after ML385 treatment. In the in vitro study, overexpression of oxidative stress factors in ethanol-treated PC12 cells was inhibited by irisin treatment; however, the prevention was reversed after the knockdown of Nrf2 siRNA. Moreover, ethanol-induced overexpression of in ammatory mediators in BV2 cells was also inhibited by irisin treatment. Irisin improved depressive and anxiety-like behaviors induced by ethanol addiction/withdrawal in mice, and this protection was greatly associated with the NF-κB-mediated antiin ammatory signaling pathway and Nrf2-mediated antioxidative stress signaling pathway.

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Apelin-13 attenuates spatial memory impairment by anti-oxidative, anti-apoptosis, and anti-inflammatory mechanism against ethanol neurotoxicity in the neonatal rat hippocampus

Cited by 12 publications

References 66 publications

The Fetal Alcohol Spectrum Disorders—An Overview of Experimental Models, Therapeutic Strategies, and Future Research Directions

The Fetal Alcohol Spectrum Disorders—An Overview of Experimental Models, Therapeutic Strategies, and Future Research Directions

The Yin and Yang Effect of the Apelinergic System in Oxidative Stress

Irisin attenuates ethanol-induced behavioral deficits in mice through activation of Nrf2 and inhibition of NF-κB pathways

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