Thioredoxin is not a marker for treatment-resistance depression but associated with cognitive function: An rTMS study

Aydın, Efruz Pirdoğan; Genç, Abdullah; Dalkıran, Mihriban; Uyar, Ece Türkyılmaz; İpek, Deniz; Özer, Ömer; Karamustafalıoğlu, K. Oğuz

doi:10.1016/j.pnpbp.2017.04.025

Cited by 19 publications

(7 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proposed biomarkers include neuroimaging biomarkers, such as those for functional magnetic resonance imaging (Lener and Iosifescu, 2015; Drysdale et al, 2017), genomic markers (Licinio et al, 2009; Lin et al, 2014) or levels of molecules in the blood, such as proteins (i.e., cytokines, neurotrophins, and/or their receptors), mRNAs, or miRNAs (Cattaneo et al, 2016; Maffioletti et al, 2016; Siwek et al, 2017). In our study, several proteins detected in sEVs after both restraint and immobilization have already been proposed as markers of depressive disorders or of their symptoms, such as thioredoxin, a redox protein that protects against oxidative stress (Aydin et al, 2018), or the voltage-dependent anion selective ion channels that regulate mitochondrial cytochrome c release (Glombik et al, 2015). A large proportion of the differential proteome identified here participates in the regulation of mitochondrial function and oxidative stress, supporting the implication of energy metabolism changes (especially oxidative phosphorylation and glycolysis) in stress-associated disorders (Corena-McLeod et al, 2013; Detka et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Small Extracellular Vesicles in Rat Serum Contain Astrocyte-Derived Protein Biomarkers of Repetitive Stress

Gómez-Molina

Sandoval

Henzi

et al. 2018

International Journal of Neuropsychopharmacology

View full text Add to dashboard Cite

Background Stress precipitates mood disorders, characterized by a range of symptoms present in different combinations, suggesting the existence of disease subtypes. Using an animal model, we previously described that repetitive stress via restraint or immobilization induced depressive-like behaviors in rats that were differentially reverted by a serotonin- or noradrenaline-based antidepressant drug, indicating that different neurobiological mechanisms may be involved. The forebrain astrocyte protein aldolase C, contained in small extracellular vesicles, was identified as a potential biomarker in the cerebrospinal fluid; however, its specific origin remains unknown. Here, we propose to investigate whether serum small extracellular vesicles contain a stress-specific protein cargo and whether serum aldolase C has a brain origin. Methods We isolated and characterized serum small extracellular vesicles from rats exposed to restraint, immobilization, or no stress, and their proteomes were identified by mass spectrometry. Data available via ProteomeXchange with identifier PXD009085 were validated, in part, by western blot. In utero electroporation was performed to study the direct transfer of recombinant aldolase C-GFP from brain cells to blood small extracellular vesicles. Results A differential proteome was identified among the experimental groups, including aldolase C, astrocytic glial fibrillary acidic protein, synaptophysin, and reelin. Additionally, we observed that, when expressed in the brain, aldolase C tagged with green fluorescent protein could be recovered in serum small extracellular vesicles. Conclusion The protein cargo of serum small extracellular vesicles constitutes a valuable source of biomarkers of stress-induced diseases, including those characterized by depressive-like behaviors. Brain-to-periphery signaling mediated by a differential molecular cargo of small extracellular vesicles is a novel and challenging mechanism by which the brain might communicate health and disease states to the rest of the body.

show abstract

Section: Discussionmentioning

confidence: 99%

Small Extracellular Vesicles in Rat Serum Contain Astrocyte-Derived Protein Biomarkers of Repetitive Stress

Gómez-Molina

Sandoval

Henzi

et al. 2018

International Journal of Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

“…Recent evidence from human studies suggests that the thioredoxin system has a pivotal role in preserving brain integrity and cognitive function [32][33][34]. Our ndings providing new insights into the causative role of TXNIP, and conclude that TXNIP is required for age-linked neuro-in ammation through NLRP3-in ammasome activation.…”

Section: Discussionmentioning

confidence: 53%

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

Ismael¹,

Nasoohi²,

Yoo³

et al. 2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

“…However, there are different views on the anti-depressant effect of rTMS through anti-oxidative stress. Aydın et al [ 27 ] found that there was no difference in serum thioredoxin, a protein with anti-oxidant function, between healthy and TRD patients, or between TRD patients before and after rTMS treatment.…”

Section: Anti-oxidative Stress Effectsmentioning

confidence: 99%

Mechanisms of repetitive transcranial magnetic stimulation for anti-depression: Evidence from preclinical studies

Luan

Zhao

Shi

et al. 2020

WJP

View full text Add to dashboard Cite

This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies, including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway, anti-oxidative stress effects, enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway, increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway, and reducing the activity of the hypothalamic-pituitary-adrenocortical axis. We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning, shallow depth of stimulation, and difficulty in elucidating the neural circuit mechanism up- and down-stream of the stimulation target brain region.

show abstract

Thioredoxin is not a marker for treatment-resistance depression but associated with cognitive function: An rTMS study

Cited by 19 publications

References 82 publications

Small Extracellular Vesicles in Rat Serum Contain Astrocyte-Derived Protein Biomarkers of Repetitive Stress

Small Extracellular Vesicles in Rat Serum Contain Astrocyte-Derived Protein Biomarkers of Repetitive Stress

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

Mechanisms of repetitive transcranial magnetic stimulation for anti-depression: Evidence from preclinical studies

Contact Info

Product

Resources

About