scholarly journals Mechanisms of Metal-Induced Mitochondrial Dysfunction in Neurological Disorders

Toxics ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 142
Author(s):  
Hong Cheng ◽  
Bobo Yang ◽  
Tao Ke ◽  
Shaojun Li ◽  
Xiaobo Yang ◽  
...  
Keyword(s):  
Nervous System ◽  
Mitochondrial Dysfunction ◽  
Neurological Disorders ◽  
Brain Function ◽  
Energy Production ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Oxygen Species ◽  
Subsequent Decrease ◽  
The Brain

Metals are actively involved in multiple catalytic physiological activities. However, metal overload may result in neurotoxicity as it increases formation of reactive oxygen species (ROS) and elevates oxidative stress in the nervous system. Mitochondria are a key target of metal-induced toxicity, given their role in energy production. As the brain consumes a large amount of energy, mitochondrial dysfunction and the subsequent decrease in levels of ATP may significantly disrupt brain function, resulting in neuronal cell death and ensuing neurological disorders. Here, we address contemporary studies on metal-induced mitochondrial dysfunction and its impact on the nervous system.

scholarly journals Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation

2016 ◽  
Vol 84 (5) ◽  
pp. 1615-1632 ◽  
Author(s):  
Anke Osterloh ◽  
Stefanie Papp ◽  
Kristin Moderzynski ◽  
Svenja Kuehl ◽  
Ulricke Richardt ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Rickettsia Typhi ◽  
Content Type ◽  
Inflammatory Phenotype ◽  
Obligate Intracellular Bacteria ◽  
Immunocompromised Mice ◽  
The Brain

Rickettsioses are emerging febrile diseases caused by obligate intracellular bacteria belonging to the familyRickettsiaceae. Rickettsia typhibelongs to the typhus group (TG) of this family and is the causative agent of endemic typhus, a disease that can be fatal. In the present study, we analyzed the course ofR. typhiinfection in C57BL/6 RAG1−/−mice. Although these mice lack adaptive immunity, they developed only mild and temporary symptoms of disease and survivedR. typhiinfection for a long period of time. To our surprise, 3 to 4 months after infection, C57BL/6 RAG1−/−mice suddenly developed lethal neurological disorders. Analysis of these mice at the time of death revealed high bacterial loads, predominantly in the brain. This was accompanied by a massive expansion of microglia and by neuronal cell death. Furthermore, high numbers of infiltrating CD11b+macrophages were detectable in the brain. In contrast to the microglia, these cells harboredR. typhiand showed an inflammatory phenotype, as indicated by inducible nitric oxide synthase (iNOS) expression, which was not observed in the periphery. Having shown thatR. typhipersists in immunocompromised mice, we finally asked whether the bacteria are also able to persist in resistant C57BL/6 and BALB/c wild-type mice. Indeed,R. typhicould be recultivated from lung, spleen, and brain tissues from both strains even up to 1 year after infection. This is the first report demonstrating persistence and reappearance ofR. typhi, mainly restricted to the central nervous system in immunocompromised mice.

Sirtuin 5-Mediated Lysine Desuccinylation Protects Mitochondrial Metabolism Following Subarachnoid Hemorrhage in Mice

Stroke ◽  
2021 ◽  
Vol 52 (12) ◽  
pp. 4043-4053
Author(s):  
Zhi-Peng Xiao ◽  
Tao Lv ◽  
Pin-Pin Hou ◽  
Anatol Manaenko ◽  
Yuandong Liu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Atp Synthase ◽  
Citrate Synthase ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Oxygen Species ◽  
Lysine Succinylation ◽  
Brain Ph ◽  
The Brain

Background and Purpose: Sirt5 (Sirtuin 5) desuccinylates multiple metabolic enzymes and plays an important role in maintaining energy homeostasis. The goal of this study was to determine whether Sirt5-mediated desuccinylation restores the energy metabolism and protects brain against subarachnoid hemorrhage (SAH). Methods: Male C57BL/6 or Sirt5 −/− mice were used. The endovascular perforation SAH model was applied. Protein lysine succinylation in the brain cortex was examined using liquid chromatography-tandem mass spectrometry analysis. The brain metabolism was evaluated by measurement of brain pH as well as ATP and reactive oxygen species level. Neuronal cell death and neurobehavioral deficits were assessed 24 hours after SAH. The expression and desuccinylation activity of Sirt5, lysine succinylation of citrate synthase and ATP synthase subunits were investigated by Western blot, immunohistochemistry, and ELISA in SAH mice and patients. Furthermore, the benefits of resveratrol-mediated Sirt5 activation were investigated. Results: A total of 211 lysine succinylation sites were differentially expressed on 170 proteins in mice brain after SAH. Thirty-nine percent of these succinylated proteins were localized in mitochondria and they are related to energy metabolism. SAH caused a decrease of Sirt5 expression and succinylated citrate synthase as well as the subunits of ATP synthase, subsequently lowered brain pH, reduced ATP and increased reactive oxygen species production, leading to neuronal cell death, and neurological deficits. Knockdown of Sirt5 aggravated SAH-induced effects, mentioned above. Administration of resveratrol resulted in activation of Sirt5. The activation was accompanied both with restoration of the mitochondrial metabolism and alleviation of early brain injury as well as with desuccinylating citrate synthase and ATP synthase. Conclusions: Protein lysine succinylation is a biochemical hallmark of metabolic crisis after SAH, and disruption of lysine succinylation through activation of Sirt5 might be a promising therapeutic strategy for the treatment of SAH.

Brain Protection by Erythropoietin: A Manifold Task

Physiology ◽  
2008 ◽  
Vol 23 (5) ◽  
pp. 263-274 ◽  
Author(s):  
Tamer Rabie ◽  
Hugo H. Marti
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Dominant Role ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Brain Protection ◽  
Hematopoietic Growth Factors ◽  
The Central Nervous System ◽  
The Brain

Many hematopoietic growth factors are produced locally in the brain. Among these, erythropoietin (Epo), has a dominant role for neuroprotection, neurogenesis, and acting as a neurotrophic factor in the central nervous system. These functions make erythropoietin a good candidate for treating diseases associated with neuronal cell death.

scholarly journals Neuroprotective Role of Polyphenols in Treatment of Neurological Disorders: A Review

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Mudasir Maqbool ◽  
Mehrukh Zehravi
Keyword(s):  
Neurological Disorders ◽  
Elderly Population ◽  
Brain Activity ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Genetic Mutations ◽  
Biological Processes ◽  
Oxygen Species ◽  
Harmful Effects

: The most frequent illnesses characterized by the gradual malfunctioning of brain neurons are neurodegenerative disorders (NDs). Genetic mutations and a range of biological processes can produce NDs. Alzheimer's disease (AD), Parkinson's disease (PD), and Multiple Sclerosis (MS) are all related to oxidative stress (OS). Reduced brain activity has become a greater health threat with a growing elderly population. It causes some pathophysiological alterations and is an important risk factor for a range of neurodegenerative illnesses. An increase in reactive oxygen species (ROS) can cause neuronal cell death, and it is thus essential to control ROS levels to maintain normal neuronal activity. Synthetic medicines are often used to treat neurological disorders; however, harmful effects have been reported. Multiple bodies of research have shown the effectiveness of polyphenols in the treatment of various NDs due to their negligible side effects. This review article describes the neuroprotection effects of polyphenols such as resveratrol, epigallocatechin-3-gallate, curcumin, and quercetin, as well as the signaling pathways and immune response controls through polyphenols.

Oxidative Stress: Major Threat in Traumatic Brain Injury

2018 ◽  
Vol 17 (9) ◽  
pp. 689-695 ◽  
Author(s):  
Nidhi Khatri ◽  
Manisha Thakur ◽  
Vikas Pareek ◽  
Sandeep Kumar ◽  
Sunil Sharma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mitochondrial Dysfunction ◽  
Calcium Influx ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Physical Assault ◽  
Mortality And Morbidity ◽  
Primary Injury

Background & Objective: Traumatic Brain Injury (TBI) is one of the major causes of mortality and morbidity worldwide. It represents mild, moderate and severe effects of physical assault to brain which may cause sequential, primary or secondary ramifications. Primary injury can be due to the first physical hit, blow or jolt to one of the brain compartments. The primary injury is then followed by secondary injury which leads to biochemical, cellular, and physiological changes like blood brain barrier disruption, inflammation, excitotoxicity, necrosis, apoptosis, mitochondrial dysfunction and generation of oxidative stress. Apart from this, there is also an immediate increase in glutamate at the synapses following severe TBI. Excessive glutamate at synapses in turn activates corresponding NMDA and AMPA receptors that facilitate excessive calcium influx into the neuronal cells. This leads to the generation of oxidative stress which further leads to mitochondrial dysfunction, lipid peroxidation and oxidation of proteins and DNA. As a consequence, neuronal cell death takes place and ultimately people start facing some serious disabilies. Conclusion: In the present review we provide extensive overview of the role of reactive oxygen species (ROS)-induced oxidative stress and its fatal effects on brain after TBI.

scholarly journals Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1702
Author(s):  
Sereen Sandouka ◽  
Tawfeeq Shekh-Ahmad
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Status Epilepticus ◽  
Temporal Lobe Epilepsy ◽  
Antioxidant Capacity ◽  
Temporal Lobe ◽  
Epileptiform Activity ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
The Brain

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.

Gut–brain axis biochemical signalling from the gastrointestinal tract to the central nervous system: gut dysbiosis and altered brain function

2018 ◽  
Vol 94 (1114) ◽  
pp. 446-452 ◽  
Author(s):  
Borros M Arneth
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Function ◽  
Well Being ◽  
Immune System Activation ◽  
Published Evidence ◽  
Bidirectional Communication ◽  
The Central Nervous System ◽  
Intestinal Functions ◽  
The Brain

BackgroundThe gut–brain axis facilitates a critical bidirectional link and communication between the brain and the gut. Recent studies have highlighted the significance of interactions in the gut–brain axis, with a particular focus on intestinal functions, the nervous system and the brain. Furthermore, researchers have examined the effects of the gut microbiome on mental health and psychiatric well-being.The present study reviewed published evidence to explore the concept of the gut–brain axis.AimsThis systematic review investigated the relationship between human brain function and the gut–brain axis.MethodsTo achieve these objectives, peer-reviewed articles on the gut–brain axis were identified in various electronic databases, including PubMed, MEDLINE, CIHAHL, Web of Science and PsycINFO.ResultsData obtained from previous studies showed that the gut–brain axis links various peripheral intestinal functions to brain centres through a broad range of processes and pathways, such as endocrine signalling and immune system activation. Researchers have found that the vagus nerve drives bidirectional communication between the various systems in the gut–brain axis. In humans, the signals are transmitted from the liminal environment to the central nervous system.ConclusionsThe communication that occurs in the gut–brain axis can alter brain function and trigger various psychiatric conditions, such as schizophrenia and depression. Thus, elucidation of the gut–brain axis is critical for the management of certain psychiatric and mental disorders.

scholarly journals Neuroprotective Effects of Gagam-Sipjeondaebo-Tang, a Novel Herbal Formula, against MPTP-Induced Parkinsonian Mice and MPP+-Induced Cell Death in SH-SY5Y Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jade Heejae Ko ◽  
Ju-Hee Lee ◽  
Bobin Choi ◽  
Ju-Yeon Park ◽  
Young-Won Kwon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Apoptotic Cell ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Motor Dysfunction ◽  
Herbal Formula ◽  
Neuroprotective Effects

Parkinson’s disease is a neurodegenerative disease characterized by progressive cell death of dopaminergic neuron and following neurological disorders. Gagam-Sipjeondaebo-Tang (GST) is a novel herbal formula made of twelve medicinal herbs derived from Sipjeondaebo-Tang, which has been broadly used in a traditional herbal medicine. In the present study, we investigated the effects of GST against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor abnormalities in mice and 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in SH-SY5Y cell. First, we found that GST alleviated motor dysfunction induced by MPTP, and the result showed dopaminergic neurons recovery in substantia nigra. In the cell experiment, pretreatment with GST increased the cell viability and attenuated apoptotic cell death in MPP+-treated SH-SY5Y cells. GST also inhibited reactive oxygen species production and restored the mitochondrial membrane potential loss, which were induced by MPP+. Furthermore, GST extract significantly activated ERK and Akt, cell survival-related proteins, in SH-SY5Y cells. The effect of GST preventing mitochondrial dysfunction was antagonized by pretreatment of PD98059 and LY294002, selective inhibitors of ERK and Akt, respectively. Taken together, GST alleviated abnormal motor functions and recovered neuronal cell death, mitochondrial dysfunction, possibly via ERK and Akt activation. Therefore, we suggest that GST may be a candidate for the treatment and prevention of Parkinson’s disease.

Introductory remarks

1980 ◽  
Vol 210 (1178) ◽  
pp. 3-4 ◽  
Keyword(s):  
Nervous System ◽  
Brain Function ◽  
Specific Receptor ◽  
Morphine Group ◽  
Neural Origin ◽  
Long Time ◽  
The Central Nervous System ◽  
Pressor Activity ◽  
Short Time ◽  
The Brain

It was in 1895 that Oliver & Schafer discovered the pressor activity of glycerol extracts of the pituitary. By 1928 it was clear that this activity, called vasopressin, was due to a peptide derived from the neural lobes of the pituitary and, in the early fifties, its structure and that of its ‘twin’, oxytocin, were determined by du Vigneaud and his colleagues, who were also able to prepare them synthetically. For a long time these two peptides, which were clearly of neural origin, were thought to have only peripheral physiological actions. However, evidence has gradually accumulated that these as well as some hormonal peptides not of neural origin, such as angiotensin and corticotrophin, could have actions on the central nervous system. The discovery of the enkephalins by Hughes & Kosterlitz in 1975 revealed the presence of an oligopeptide in the forebrain that could influence brain function and for which a specific receptor could be delineated which provided an immediate connection with the well documented non-peptide analgesic drugs of the morphine group. Within a short time discrete localization both of enkaphalin stores and of enkephalin receptors within the nervous system was demonstrated. In the ensuing period a growing number of peptides have either been isolated from the brain or have been inferred, from immunological evidence, to be present. Some of these peptides, such as insulin and gastrin, have well established peripheral biological actions, and their presence in the brain has engendered considerable surprise.

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