Abstract
Many neurodegenerative diseases have several similar cellular dysregulations. We investigated the inhibitory role of Ishige okamurae, an edible brown alga, on neurodegenerative processes by estimating the effects of Ishige okamurae on excitotoxicity induced by glutamate in vitro and neurodegeneration induced by trimethyltin (TMT) in vivo. This study aimed to describe the molecular mechanisms responsible for the mediating anti-neurodegenerative effects of Ishige okamurae extract (IOE). The oral administration of IOE to TMT-injected mice impeded the TMT-mediated short- and long-term memory impairments investigated by the Morris water maze and Y-maze test. IOE attenuated TMT-mediated cellular apoptosis and the expression of brain-derived neurotrophic factor, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in mice brains. Glutamate-induced apoptosis and the expression of reactive oxygen species, Nrf2, and HO-1 in HT22 cells were also attenuated by IOE. In addition, TMT- and glutamate-induced phosphorylation of mitogen-activated protein kinases (MAPKs) in mouse brain tissues and HT22 cells were attenuated by the treatment of IOE. In HT22 cells, administration of MAPK inhibitors recovered the glutamate induced by the expression of Nrf2, HO-1, and cellular dysregulation to the equal extent to IOE administration. Taken together, these results suggest that IOE could attenuate neurodegenerative processes, such as TMT- and glutamate-mediated neuronal dysregulation, by regulating MAPKs/Nrf-2/HO-1 antioxidant pathways.
Highlights
Neurodegeneration is the progressive functional or structural loss of neurons that results in many incurable neurodegenerative diseases, such as Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, fatal familial insomnia, and Alzheimer’s disease
For investigating the effects of Ishige okamurae extract (IOE) on TMT-mediated cognitive deficits, IOE (20 mg/kg bw/day) was orally administrated for three weeks and TMT was intraperitoneally injected into mice (Figure 1A)
We found that TMT-mediated abnormal expression of heme oxygenase-1 (HO-1), which has a protective role in oxidative stress, and nuclear factor erythroid 2-related factor 2 (Nrf2), a major transcriptional factor of HO-1, were restored in the TMT + IOE mice brains
Summary
Neurodegeneration is the progressive functional or structural loss of neurons that results in many incurable neurodegenerative diseases, such as Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, fatal familial insomnia, and Alzheimer’s disease These neurodegenerative diseases have been proven to have many similar phenotypes on a sub-cellular level that give us a chance to develop therapeutics to ameliorate the neurodegenerative diseases simultaneously. For this reason, several model systems, such as TMT-induced neurodegeneration and glutamate excitotoxicity, are often used for investigating the effects of therapeutic candidates on neurodegenerative diseases.
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