Differences in the protein expression levels of Trx2 and Prx3 in the hippocampal CA1 region between adult and aged gerbils following transient global cerebral ischemia

Lee, Choong Hyun; Park, Joon Ha; Cho, Jeong‐Hwi; Ahn, Ji Hyeon; Bae, Eun Joo; Won, Moo‐Ho

doi:10.3892/mmr.2015.3760

Cited by 9 publications

(8 citation statements)

References 34 publications

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“…In agreement with earlier ndings [48,49], our aged animal brains manifested marginal TRX depletion at mRNA and protein levels, hypothetically as a consequence of TXNIP upregulation. This hypothesis was later con rmed in additional experiments showing that aged TXNIP knock-out (TXNIP −/− ) mice completely retain TRX levels.…”

Section: Discussionsupporting

confidence: 93%

TXNIP regulates age-associated neuroinflammation: Implication in Alzheimer’s disease

Ismael¹,

Nasoohi²,

Yoo³

et al. 2020

Preprint

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Background Immune system hypersensitivity with aging is believed to contribute to mental frailty in elderlies. This is postulated to arise from accumulation of oxidative molecular patterns. Solid evidences delineates thioredoxin interacting protein (TXNIP), an inducible protein involved in oxidative stress, is essential for NOD-like receptor pyrin domain containing-3 (NLRP3)-inflammasome activation which intimately connects “inflammaging” to senile cognitive decline. This study aims to fundamentally explore the plausible involvement of TXNIP/NLRP3 inflammasome pathway in senile dementia and the typical Alzhemier’s disease. Methods In experimental studies cerebral samples from gender-matched mice were compared for TXNIP/NLRP3 inflammasome activation and klotho depletion, through immunoblotting and immunostaining in different life span points. In aged males, genetic or pharmacological ablation of TXNIP were then used to determine effects on cognitive decline and sensorimotor frailty in morris water maze, novel object recognition test and gait control analysis. Immunoblotting/staining experiments were also performed on human postmortem aged hippocampal specimens and 5XFAD transgenic mice, to ultimately address Alzheimer’s disease (AD) as the most age related dementia. Results According to our preclinical studies, cerebral TXNIP was significantly upregulated in aged animals, paralleled by the NLRP3-inflammasome over-activity in both sexes, and closely associated klotho depletion in aged males. TXNIP knock-out reversed age-related NLRP3-hyperactivity and enhanced thioredoxin (TRX) levels in aged brains. Further, pharmacological TXNIP inhibition replicated the TXNIP/NLRP3-inflammasome downregulation in aged animals, with FOXO-1 and mTOR upregulation. These alterations concurred with substantial improvements in both cognitive and sensorimotor abilities. Moreover, our immunostaining shows a significant increase of TXNIP in transgenic 5XFAD mice brain and TXNIP/NLRP3-inflammasome activity in AD human postmortem hippocampal specimens, in proximity of p-tau tangles and β-amyloid plaques. Conclusion Together, these findings substantiate the pivotal role of TXNIP to drive inflammging in parallel with klotho depletion and functional decline. TXNIP co-localization with hallmarks of AD pathology is further supportive of potential mechanistic links between TXNIP and AD. Unraveling new information on upstream pathways, these data support modulating thioredoxin system as a potential approach to decelerate senile frailty.

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Section: Discussionsupporting

confidence: 93%

TXNIP regulates age-associated neuroinflammation: Implication in Alzheimer’s disease

Ismael¹,

Nasoohi²,

Yoo³

et al. 2020

Preprint

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“…We only detected a significant change in SNPs between Sham and irradiated mice on the loci for mitochondrial ROS scavengers Thioredoxin 2 and Thioredoxin 3. Interestingly, Thioredoxin 2 is a major component of the mitochondrial apoptosis-signaling pathway and glutaredoxin system, and has been found to have an increased presence in the hippocampus of aged dogs, but is lowered in the CA1 region of aged Gerbils (Tanaka, 2002;Ahn et al, 2011;Lee et al, 2015). Conversely, little has been reported of Thioredoxin 3, which appears to have low expression in the mouse brain (Sun et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Late Effects of 1H + 16O on Short-Term and Object Memory, Hippocampal Dendritic Morphology and Mutagenesis

Kiffer

Alexander

Anderson

et al. 2020

Front. Behav. Neurosci.

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The space extending beyond Earth's magnetosphere is subject to a complex field of high-energy charged nuclei, which are capable of traversing spacecraft shielding and human tissues, inducing dense ionization events. The central nervous system is a major area of concern for astronauts who will be exposed to the deep-space radiation environment on a mission to Mars, as charged-particle radiation has been shown to elicit changes to the dendritic arbor within the hippocampus of rodents, and related cognitive-behavioral deficits. We exposed 6-month-old male mice to whole-body 1 H (0.5 Gy; 150 MeV/n; 18-19 cGy/minute) and an hour later to 16 O (0.1Gy; 600 MeV/n; 18-33 Gy/min) at NASA's Space Radiation Laboratory as a galactic cosmic ray-relevant model. Animals were housed with bedding which provides cognitive enrichment. Mice were tested for cognitive behavior 9 months after exposure to elucidate late radiation effects. Radiation induced significant deficits in novel object recognition and short-term spatial memory (Y-maze). Additionally, we observed opposing morphological differences between the mature granular and pyramidal neurons throughout the hippocampus, with increased dendritic length in the dorsal dentate gyrus and reduced length and complexity in the CA1 subregion of the hippocampus. Dendritic spine analyses revealed a severe reduction in mushroom spine density throughout the hippocampus of irradiated animals. Finally, we detected no general effect of radiation on single-nucleotide polymorphisms in immediate early genes, and genes involved in inflammation but found a higher variant allele frequency in the antioxidants thioredoxin reductase 2 and 3 loci.

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“…Recently, substantial evidence has indicated that the Trx and Prx redox system is associated with neuronal damage and neuroprotective effects via the regulation of oxidative stress in brain ischemia (Hwang et al, 2010; Lee et al, 2015). To gain additional evidence for sevoflurane post-conditioning-induced neuroprotection against cerebral ischemia, the expression level of several proteins normally enriched in mitochondria was investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Peroxiredoxin 3 (Prx3) is exclusively found in mitochondria and plays a role in the antioxidant defense system and homeostasis within mitochondria (Hwang et al, 2010; Du et al, 2014). Thioredoxin 2 (Trx2) is expressed with a mitochondrial leading sequence and transported specifically into mitochondria, playing an essential role in cell survival and mitochondria-mediated apoptosis (Ma et al, 2013; Lee et al, 2015). Among the subtypes of Trx and Prx, Prx3 and Trx2 are exclusively expressed in the mitochondrial compartment, and are involved in the control of the antioxidant defense system, cell survival, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…However, the mechanism of sevoflurane's protective effect on cerebral ischemia in the context of mitochondrial dysfunction has not been well-investigated. Additionally, recent studies demonstrated that some specific antioxidant enzymes are located in mitochondria, such as heat shock protein 60 (HSP60), peroxiredoxin 3 (Prx3), and thioredoxin 2 (Trx2), which protect mitochondria against ROS-induced damage by catalyzing the reduction of H 2 O 2 into water (Hwang et al, 2010; Lee et al, 2015). So far, it has not been well-established in a global cerebral ischemic model whether these mitochondria-specific antioxidant enzymes in the hippocampus mediates the neuroprotective effect of sevoflurane.…”

Section: Introductionmentioning

confidence: 99%

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Sevoflurane Post-conditioning Enhanced Hippocampal Neuron Resistance to Global Cerebral Ischemia Induced by Cardiac Arrest in Rats through PI3K/Akt Survival Pathway

Wang

Zhi

Huang

et al. 2016

Front. Cell. Neurosci.

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The purpose of this current study was to evaluate whether improvement of mitochondrial dysfunction was involved in the therapeutic effect of sevoflurane post-conditioning in global cerebral ischemia after cardiac arrest (CA) via the PI3K/Akt pathway. In the first experiment, animals were randomly divided into three groups: a sham group, a CA group, a CA+sevoflurane post-conditioning group (CA+SE). Sevoflurane post-conditioning was achieved by administration of 2.5% sevoflurane for 30 min after resuscitation. Sevoflurane post-conditioning has a significant neuroprotective effect by increasing survival rates and reducing neuronal apoptosis. Additionally, the gene and protein expression of PGC-1α, NRF-1, and TFAM, the master regulators of mitochondrial biogenesis, were up-regulated in the CA+SE group, when compared to the CA group. Similarly, in contrast to the CA group, mitochondria-specific antioxidant enzymes, including heat-shock protein 60 (HSP60), peroxiredoxin 3 (Prx3), and thioredoxin 2 (Trx2) were also increased in the CA+SE group. Finally, administration of sevoflurane ameliorated mitochondrial reactive oxygen species (ROS) formation and maintained mitochondrial integrity. In the second experiment, we investigated the relationship between the PI3K/Akt pathway and mitochondrial biogenesis and mitochondria-specific antioxidant enzymes in sevoflurane-induced neuroprotection. The selective PI3K inhibitor wortmannin not only eliminated the beneficial biochemical processes of sevoflurane by reducing the level of mitochondrial biogenesis-related proteins and aggravating mitochondrial integrity, but also reversed the elevation of mitochondria-specific antioxidant enzymes induced by sevoflurane. Therefore, our data suggested that sevoflurane post-conditioning provides neuroprotection via improving mitochondrial biogenesis and integrity, as well as increasing mitochondria-specific antioxidant enzymes by a mechanism involving the PI3K/Akt pathway.

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Differences in the protein expression levels of Trx2 and Prx3 in the hippocampal CA1 region between adult and aged gerbils following transient global cerebral ischemia

Cited by 9 publications

References 34 publications

TXNIP regulates age-associated neuroinflammation: Implication in Alzheimer’s disease

TXNIP regulates age-associated neuroinflammation: Implication in Alzheimer’s disease

Late Effects of 1H + 16O on Short-Term and Object Memory, Hippocampal Dendritic Morphology and Mutagenesis

Sevoflurane Post-conditioning Enhanced Hippocampal Neuron Resistance to Global Cerebral Ischemia Induced by Cardiac Arrest in Rats through PI3K/Akt Survival Pathway

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