Abstract
Oxidative stress is known to be critically implicated in the pathophysiology of several neurological disorders, including Alzheimer’s disease and ischemic stroke. The remarkable neurotrophic activity of Gelidium amansii, which has been reported consistently in a series of our previous studies, inspired us to investigate whether this popular agarophyte could protect against hypoxia/reoxygenation (H/R)-induced oxidative injury in hippocampal neurons. The primary culture of hippocampal neurons challenged with H/R suffered from a significant loss of cell survival, accompanied by apoptosis and necrosis, DNA damage, generation of reactive oxygen species (ROS), and dissipation of mitochondrial membrane potential (ΔΨm), which were successfully attenuated when the neuronal cultures were preconditioned with ethanolic extract of G. amansii (GAE). GAE also attenuated an H/R-mediated increase of BAX and caspase 3 expressions while promoting Bcl-2 expression. Moreover, the expression of N-methyl-d-acetate receptor subunit 2B (GluN2B), an extrasynaptic glutamate receptor, was significantly repressed, while synaptic GluN2A expression was preserved in GAE-treated neurons as compared to those without GAE intervention. Together, this study demonstrates that GAE attenuated H/R-induced oxidative injury in hippocampal neurons through, at least in part, a potential neuroprotective mechanism that involves inhibition of GluN2B-mediated excitotoxicity and suppression of ROS production, and suggests that this edible seaweed could be a potential source of bioactive metabolites with therapeutic significance against oxidative stress-related neurodegeneration, including ischemic stroke and neurodegenerative diseases.
Highlights
Ischemia/reperfusion (I/R) installs a cascade of pathological events that culminate in several clinical conditions, including ischemic stroke and degenerative brain disease [1]
With high metabolic demand and peroxidizable lipid contents, neurons are potentially vulnerable to I/R-induced oxidative injury, which is accompanied by apoptosis, necrosis, and DNA
Cytotoxicity analysis whether GAE showed any toxic effects in the cultured neurons under normoxic conditions
Summary
Ischemia/reperfusion (I/R) installs a cascade of pathological events that culminate in several clinical conditions, including ischemic stroke and degenerative brain disease [1]. The I/R provokes a deleterious mechanism that involves excess production of reactive oxygen species (ROS), resulting in the oxidative. Antioxidants 2020, 9, 223 stress in cells [2]. Mitochondria play a critical role in initiating apoptosis through contributing excess ROS generation. During I/R, there is an involvement of glutamate excitotoxicity, to which the expression of extrasynaptic glutamate receptors such as GluN2B has been crucially implicated. This I/R-induced excitotoxicity initiates a cascade mechanism that results in the cellular oxidative stress and loss of mitochondrial membrane potential (∆Ψm ). Targeting excitotoxicity-mediated oxidative stress might, be a potential therapeutic strategy in neurodegenerative diseases
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