scholarly journals The Role of AhR in the Hallmarks of Brain Aging: Friend and Foe

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2729
Author(s):  
Emmanuel S. Ojo ◽  
Shelley A. Tischkau
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Aging Process ◽  
Cell Activation ◽  
Brain Aging ◽  
Aryl Hydrocarbon ◽  
Glial Cell Activation ◽  
The Impact ◽  
The Brain

In recent years, aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered to be involved in aging phenotypes across several species. This receptor is a highly conserved biosensor that is activated by numerous exogenous and endogenous molecules, including microbiota metabolites, to mediate several physiological and toxicological functions. Brain aging hallmarks, which include glial cell activation and inflammation, increased oxidative stress, mitochondrial dysfunction, and cellular senescence, increase the vulnerability of humans to various neurodegenerative diseases. Interestingly, many studies have implicated AhR signaling pathways in the aging process and longevity across several species. This review provides an overview of the impact of AhR pathways on various aging hallmarks in the brain and the implications for AhR signaling as a mechanism in regulating aging-related diseases of the brain. We also explore how the nature of AhR ligands determines the outcomes of several signaling pathways in brain aging processes.

scholarly journals Peripheral blood exosomes pass blood-brain-barrier and induce glial cell activation

2018 ◽  
Author(s):  
Diana M. Morales-Prieto ◽  
Milan Stojiljkovic ◽  
Celia Diezel ◽  
Priska-Elisabeth Streicher ◽  
Franziska Röstel ◽  
...  
Keyword(s):  
Glial Cell ◽  
Blood Brain Barrier ◽  
Cell Activation ◽  
Cell Function ◽  
Brain Aging ◽  
Extracellular Vesicle ◽  
Brain Barrier ◽  
Blood Brain ◽  
Glial Cell Activation

ABSTRACTBackgroundExosomes are involved in intracellular communication and contain proteins, mRNAs, miRNAs, and signaling molecules. Exosomes were shown to act as neuroinflammatory mediators involved in neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS). Brain aging has been associated to increased neuroinflammation. In addition, a decreased extracellular vesicle concentration was observed in aging tissues. The specific mechanisms how exosomes and aging are connected are not known yet.ResultsHere we have shown that peripheral injection had almost no effect on selected gene expression in the liver. However, exosome injection has led to changes in the specific markers of glial cell activation (CD68, Iba1, GFAP). Interestingly, only injection of exosomes isolated from aged mice induced significant activation of astrocyte cells, as shown by increased GFAP expression.ConclusionTranscription levels of genes GFAP, TGF-β, CD68, Iba1 known to be involved in glial cell function are significantly changing after introduction of peripheral extracellular vesicles. Exosomes were able to pass blood brain barrier and induce glial cell activation. GFAP known to be a specific astrocyte activation marker was significantly higher expressed after injection of old but not young exosomes, indicating a possible role of exosomes in the mechanisms of brain aging.

scholarly journals Does COVID-19 Affect Adult Neurogenesis? A Neurochemical Perspective

2021 ◽  
Author(s):  
Jayakumar Saikarthik ◽  
Ilango Saraswathi ◽  
Abdulrahman A. Al-Atram
Keyword(s):  
Adult Neurogenesis ◽  
Cell Activation ◽  
Immune Cell ◽  
Neuropsychiatric Symptoms ◽  
Brain Regions ◽  
Immune Cell Activation ◽  
Brain Involvement ◽  
The Impact ◽  
The Brain

COVID-19 has been found to cause neuropsychiatric symptoms which indicate brain involvement. SARS-CoV-2 may enter the brain by damaging and penetrating olfactory mucosa and via other possible routes like damaged blood–brain barrier, and hematologic spread. With SARS-CoV-2 having a higher affinity to ACE2 receptors, brain regions that have higher ACE2 receptors like the hippocampus, are more vulnerable to the effect of the viral invasion. In addition, immune cell activation, an important feature of COVID-19, leads to cytokine storm which causes neurotoxicity, neuroinflammation, and neurodegeneration. Impaired adult neurogenesis is related to many psychiatric disorders including depression, bipolar disorder, anxiety disorder, schizophrenia, and PTSD. It is known to be related to the depletion of neurotransmitters, dopamine, serotonin, norepinephrine, GABA, and glutamate which play a major role in adult neurogenesis. A recent study reveals that SSRI which acts by increasing serotonin is proven beneficial in COVID-19 patients. Thus, the current chapter will discuss the impact of COVID-19 on adult neurogenesis with emphasis on the role of ACE2 and neurotransmitters.

Biomechanistic insights into the roles of oxidative stress in generating complex neurological disorders

2018 ◽  
Vol 399 (4) ◽  
pp. 305-319 ◽  
Author(s):  
Mohammad Yusuf ◽  
Maria Khan ◽  
Majed A. Robaian ◽  
Riaz A. Khan
Keyword(s):  
Oxidative Stress ◽  
Neurological Disorders ◽  
Cell Activation ◽  
Enzyme System ◽  
Neurological Diseases ◽  
Excess Oxygen ◽  
Antioxidant Enzyme System ◽  
Glial Cell Activation ◽  
The Brain ◽  
Lateral Sclerosis

AbstractNeurological diseases like Alzheimer’s disease, epilepsy, parkinsonism, depression, Huntington’s disease and amyotrophic lateral sclerosis prevailing globally are considered to be deeply influenced by oxidative stress-based changes in the biochemical settings of the organs. The excess oxygen concentration triggers the production of reactive oxygen species, and even the intrinsic antioxidant enzyme system, i.e. SOD, CAT and GSHPx, fails to manage their levels and keep them under desirable limits. This consequently leads to oxidation of protein, lipids and nucleic acids in the brain resulting in apoptosis, proteopathy, proteasomes and mitochondrion dysfunction, glial cell activation as well as neuroinflammation. The present exploration deals with the evidence-based mechanism of oxidative stress towards development of key neurological diseases along with the involved biomechanistics and biomaterials.

scholarly journals Antioxidants Promote Intestinal Tumor Progression in Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 241
Author(s):  
Zhiyuan V. Zou ◽  
Kristell Le Gal ◽  
Ahmed E. El Zowalaty ◽  
Lara E. Pehlivanoglu ◽  
Viktor Garellick ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Tumor Progression ◽  
Human Subjects ◽  
Plasma Concentrations ◽  
Intestinal Tumor ◽  
Adenomatous Polyposis ◽  
Intestinal Tumors ◽  
The Impact

Dietary antioxidants and supplements are widely used to protect against cancer, even though it is now clear that antioxidants can promote tumor progression by helping cancer cells to overcome barriers of oxidative stress. Although recent studies have, in great detail, explored the role of antioxidants in lung and skin tumors driven by RAS and RAF mutations, little is known about the impact of antioxidant supplementation on other cancers, including Wnt-driven tumors originating from the gut. Here, we show that supplementation with the antioxidants N-acetylcysteine (NAC) and vitamin E promotes intestinal tumor progression in the ApcMin mouse model for familial adenomatous polyposis, a hereditary form of colorectal cancer, driven by Wnt signaling. Both antioxidants increased tumor size in early neoplasias and tumor grades in more advanced lesions without any impact on tumor initiation. Importantly, NAC treatment accelerated tumor progression at plasma concentrations comparable to those obtained in human subjects after prescription doses of the drug. These results demonstrate that antioxidants play an important role in the progression of intestinal tumors, which may have implications for patients with or predisposed to colorectal cancer.

scholarly journals Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6071
Author(s):  
Suzanne Gascon ◽  
Jessica Jann ◽  
Chloé Langlois-Blais ◽  
Mélanie Plourde ◽  
Christine Lavoie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factors ◽  
Signaling Pathways ◽  
Brain Structures ◽  
Therapeutic Strategies ◽  
Native Proteins ◽  
Receptor Sites ◽  
The Brain

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

scholarly journals Infectious disease-associated encephalopathies

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Maria C. Barbosa-Silva ◽  
Maiara N. Lima ◽  
Denise Battaglini ◽  
Chiara Robba ◽  
Paolo Pelosi ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Cognitive Deficits ◽  
Brain Function ◽  
Cell Activation ◽  
Therapeutic Strategies ◽  
Barrier Dysfunction ◽  
Glial Cell Activation ◽  
The Central Nervous System ◽  
Underlying Mechanisms

AbstractInfectious diseases may affect brain function and cause encephalopathy even when the pathogen does not directly infect the central nervous system, known as infectious disease-associated encephalopathy. The systemic inflammatory process may result in neuroinflammation, with glial cell activation and increased levels of cytokines, reduced neurotrophic factors, blood–brain barrier dysfunction, neurotransmitter metabolism imbalances, and neurotoxicity, and behavioral and cognitive impairments often occur in the late course. Even though infectious disease-associated encephalopathies may cause devastating neurologic and cognitive deficits, the concept of infectious disease-associated encephalopathies is still under-investigated; knowledge of the underlying mechanisms, which may be distinct from those of encephalopathies of non-infectious cause, is still limited. In this review, we focus on the pathophysiology of encephalopathies associated with peripheral (sepsis, malaria, influenza, and COVID-19), emerging therapeutic strategies, and the role of neuroinflammation. Graphic abstract

Preserving Integrity in the Face of Performance Threat

2012 ◽  
Vol 23 (12) ◽  
pp. 1455-1460 ◽  
Author(s):  
Lisa Legault ◽  
Timour Al-Khindi ◽  
Michael Inzlicht
Keyword(s):  
Error Detection ◽  
Error Monitoring ◽  
Error Related Negativity ◽  
Threatening Information ◽  
Electrophysiological Responses ◽  
The Face ◽  
And Performance ◽  
The Impact ◽  
The Brain

Self-affirmation produces large effects: Even a simple reminder of one’s core values reduces defensiveness against threatening information. But how, exactly, does self-affirmation work? We explored this question by examining the impact of self-affirmation on neurophysiological responses to threatening events. We hypothesized that because self-affirmation increases openness to threat and enhances approachability of unfavorable feedback, it should augment attention and emotional receptivity to performance errors. We further hypothesized that this augmentation could be assessed directly, at the level of the brain. We measured self-affirmed and nonaffirmed participants’ electrophysiological responses to making errors on a task. As we anticipated, self-affirmation elicited greater error responsiveness than did nonaffirmation, as indexed by the error-related negativity, a neural signal of error monitoring. Self-affirmed participants also performed better on the task than did nonaffirmed participants. We offer novel brain evidence that self-affirmation increases openness to threat and discuss the role of error detection in the link between self-affirmation and performance.

Oxidative stress and localization status of hepatocellular transporters: Impact on bile secretion and role of signaling pathways

2021 ◽  
Author(s):  
Cecilia L. Basiglio ◽  
Fernando A. Crocenzi ◽  
Enrique Juan Sánchez Pozzi ◽  
Marcelo Gabriel Roma
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Bile Secretion

Integrative view of serpins in health and disease: the contribution of serpinA3

2020 ◽  
Author(s):  
Andrea Sanchez-Navarro ◽  
Isaac González-Soria ◽  
Rebecca Caldiño-Bohn ◽  
Norma A. Bobadilla
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Cellular Processes ◽  
Hormone Transport ◽  
Integrative View ◽  
Health And Disease ◽  
The Brain ◽  
Regulation Of Blood Pressure ◽  
Common Function

Serpins are a superfamily of proteins characterized by their common function as serine protease inhibitors. So far, 36 serpins from nine clades have been identified. These proteins are expressed in all the organs and are involved in multiple important functions such as the regulation of blood pressure, hormone transport, insulin sensitivity, and the inflammatory response. Diseases such as obesity, diabetes, cardiovascular, and kidney disorders are intensively studied to find effective therapeutic targets. Given serpins' outstanding functionality, the deficiency or overexpression of certain types of serpin have been associated with diverse pathophysiological events. In particular, we will focus on reviewing the studies evaluating the participation of serpins, and particularly SerpinA3, in diverse diseases that occur in relevant organs such as the brain, retinas, corneas, lungs, cardiac vasculature, and kidneys. In this review, we summarize the role of serpins in physiological and pathophysiological processes, as well as recent evidence on the crucial role of SerpinA3 in several pathologies. Finally, we emphasize the importance of SerpinA3 in regulating cellular processes such as angiogenesis, apoptosis, fibrosis, oxidative stress, and the inflammatory response.

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