N-Adamantyl-4-Methylthiazol-2-Amine Attenuates Glutamate-Induced Oxidative Stress and Inflammation in the Brain

Yang, Seung-Ju; Kim, Eun-A; Chang, M.-C.; Kim, Jiae; Na, Jung-Min; Choi, Soo Young; Cho, Sung‐Woo

doi:10.1007/s12640-017-9717-x

Cited by 11 publications

(29 citation statements)

References 89 publications

(101 reference statements)

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“…The pathophysiological significance of TLR9 in HF has been addressed in some studies [4, 5, 21]. Common to all these studies are that they encompass systolic HF.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice

Dhondup

Sjaastad

Sandanger

et al. 2017

Mediators of Inflammation

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Aim. Inflammation is important in heart failure (HF). The role of the immune receptor toll-like receptor 9 (TLR9) in HF is not understood and not investigated in diastolic HF. We investigated the role of TLR9 in a murine diastolic HF model caused by cardiomyocyte SERCA2a excision. Methods and Results. We crossed SERCA2a KO and TLR9 KO mice to generate four mouse lines. Tamoxifen-induced cardiomyocyte SERCA2a gene excision was carried out in mice, causing diastolic HF. After 7.6 weeks, cardiac functions and dimensions were analyzed by echocardiography and heart tissues were processed. HF mice depleted of TLR9 demonstrated reduced survival compared to SERC2a KO mice, with a median life expectancy of 58 days compared to 63 days. Both HF groups displayed increased left atrium size, lung weight, fetal gene expressions, monocyte/macrophage infiltration, and fibrosis. However, there were no significant differences between the groups. Conclusion. In mice with SERCA2a KO-induced diastolic HF, the absence of TLR9 reduced median life expectancy. The cause remains elusive, as all investigated HF parameters were unaltered. Still, these findings support a salutary role of TLR9 in some subsets of HF conditions and underline the importance for future studies on the mechanisms of TLR9 in diastolic HF.

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“…The pathophysiological significance of TLR9 in HF has been addressed in some studies [4, 5, 21]. Common to all these studies are that they encompass systolic HF.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice

Dhondup

Sjaastad

Sandanger

et al. 2017

Mediators of Inflammation

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“…Studies have examined the role of regulators, especially aquaporin-4 (AQP4), and glutamate transporter-1 (GLT-1), which are the two essential water and glutamate astrocyte buffering pathways to the brain. In several different animal models of brain insult, including models of AD [ 41 ], aging [ 42 ], epilepsy [ 43 ] and ICH [ 44 ], AQP4 expression is lessened and its polarity becomes disrupted.…”

Section: The Imbalance Of Blood-glutamate Concentration Gradient Foll...mentioning

confidence: 99%

Glutamate Efflux across the Blood–Brain Barrier: New Perspectives on the Relationship between Depression and the Glutamatergic System

et al. 2022

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Depression is a significant cause of disability and affects millions worldwide; however, antidepressant therapies often fail or are inadequate. Current medications for treating major depressive disorder can take weeks or months to reach efficacy, have troubling side effects, and are limited in their long-term capabilities. Recent studies have identified a new set of glutamate-based approaches, such as blood glutamate scavengers, which have the potential to provide alternatives to traditional antidepressants. In this review, we hypothesize as to the involvement of the glutamate system in the development of depression. We identify the mechanisms underlying glutamate dysregulation, offering new perspectives on the therapeutic modalities of depression with a focus on its relationship to blood–brain barrier (BBB) permeability. Ultimately, we conclude that in diseases with impaired BBB permeability, such as depression following stroke or traumatic brain injury, or in neurogenerative diseases, the glutamate system should be considered as a pathway to treatment. We propose that drugs such as blood glutamate scavengers should be further studied for treatment of these conditions.

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“…In vivo (animal) data focused on the direct impact of L-Glu on neuronal molecular processes that resulted in disease, such NDDs. Different animal models were used to evaluate L-Glu neurotoxicity, including albino Wistar rats (n = 22) [27,33,36,[75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93], Sprague-Dawley rats (n = 13) [56,[94][95][96][97][98][99][100][101][102][103][104][105], other rats (n = 1) [106], Swiss albino mice (n = 3) [28,93,107], wild-type mice (n = 5) [108][109][110][111][112], Kunming mice (n = 2) [113,114], CD-1 mice (n = 1) [115], Caenorhabditis elegans nematodes (n = 1)…”

Section: In Vivo Studies Evaluating L-glu Toxicitymentioning

confidence: 99%

Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review

2022

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L-glutamate (L-Glu) is a nonessential amino acid, but an extensively utilised excitatory neurotransmitter with critical roles in normal brain function. Aberrant accumulation of L-Glu has been linked to neurotoxicity and neurodegeneration. To investigate this further, we systematically reviewed the literature to evaluate the effects of L-Glu on neuronal viability linked to the pathogenesis and/or progression of neurodegenerative diseases (NDDs). A search in PubMed, Medline, Embase, and Web of Science Core Collection was conducted to retrieve studies that investigated an association between L-Glu and pathology for five NDDs: Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Together, 4060 studies were identified, of which 71 met eligibility criteria. Despite several inadequacies, including small sample size, employment of supraphysiological concentrations, and a range of administration routes, it was concluded that exposure to L-Glu in vitro or in vivo has multiple pathogenic mechanisms that influence neuronal viability. These mechanisms include oxidative stress, reduced antioxidant defence, neuroinflammation, altered neurotransmitter levels, protein accumulations, excitotoxicity, mitochondrial dysfunction, intracellular calcium level changes, and effects on neuronal histology, cognitive function, and animal behaviour. This implies that clinical and epidemiological studies are required to assess the potential neuronal harm arising from excessive intake of exogenous L-Glu.

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N-Adamantyl-4-Methylthiazol-2-Amine Attenuates Glutamate-Induced Oxidative Stress and Inflammation in the Brain

Cited by 11 publications

References 89 publications

Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice

Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice

Glutamate Efflux across the Blood–Brain Barrier: New Perspectives on the Relationship between Depression and the Glutamatergic System

Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review

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