TopicNeuroscience

oxidative stress

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45Total items

40ePosters

5Seminars

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SeminarNeuroscienceRecording

Neuroinflammation in Epilepsy: what have we learned from human brain tissue specimens ?

Eleonora Aronica

Amsterdam UMC

Oct 25, 2023

Epileptogenesis is a gradual and dynamic process leading to difficult-to-treat seizures. Several cellular, molecular, and pathophysiologic mechanisms, including the activation of inflammatory processes. The use of human brain tissue represents a crucial strategy to advance our understanding of the underlying neuropathology and the molecular and cellular basis of epilepsy and related cognitive and behavioral comorbidities, The mounting evidence obtained during the past decade has emphasized the critical role of inflammation in the pathophysiological processes implicated in a large spectrum of genetic and acquired forms of focal epilepsies. Dissecting the cellular and molecular mediators of the pathological immune responses and their convergent and divergent mechanisms, is a major requisite for delineating their role in the establishment of epileptogenic networks. The role of small regulatory molecules involved in the regulation of specific pro- and anti-inflammatory pathways and the crosstalk between neuroinflammation and oxidative stress will be addressed. The observations supporting the activation of both innate and adaptive immune responses in human focal epilepsy will be discussed and elaborated, highlighting specific inflammatory pathways as potential targets for antiepileptic, disease-modifying therapeutic strategies.

SeminarNeuroscienceRecording

Redox and mitochondrial dysregulation in epilepsy

Manisha Patel

University of Colorado

Sep 21, 2022

Epileptic seizures render the brain uniquely dependent on energy producing pathways. Studies in our laboratory have been focused on the role of redox processes and mitochondria in the context of abnormal neuronal excitability associated with epilepsy. We have shown that that status epilepticus (SE) alters mitochondrial and cellular redox status, energetics and function and conversely, that reactive oxygen species and resultant dysfunction can lead to chronic epilepsy. Oxidative stress and neuroinflammatory pathways have considerable crosstalk and targeting redox processes has recently been shown to control neuroinflammation and excitability. Understanding the role of metabolic and redox processes can enable the development of novel therapeutics to control epilepsy and/or its comorbidities.

SeminarNeuroscience

Ebselen: a lithium-mimetic without lithium side-effects?

Beata R. Godlewska

Clinical Psychopharmacology Research Group, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.

Jul 1, 2022

Development of new medications for mental health conditions is a pressing need given the high proportion of people not responding to available treatments. We hope that presenting ebselen to a wider audience will inspire further studies on this promising agent with a benign side-effects profile. Laboratory research, animal research and human studies suggest that ebselen shares many features with the mood stabilising drug lithium, creating a promise of a drug that would have a similar clinical effect but without lithium’s troublesome side-effect profile and toxicity. Both drugs have a common biological target, inositol monophosphatase, whose inhibition is thought key to lithium’s therapeutic effect. Both drugs have neuroprotective action and reduce oxidative stress. In animal studies, ebselen affected neurotransmitters involved in the development of mental health symptoms, and in particular, produced effects of serotonin function very similar to lithium. Both ebselen and lithium share behavioural effects: antidepressant-like effects in rodent models of depression and decrease in behavioural impulsivity, a property associated with lithium's anti-suicidal action. Human neuropsychological studies support an antidepressant profile for ebselen based on its positive impact on emotional processing and reward seeking. Our group currently is exploring ebselen’s effects in patients with mood disorders. A completed ‘add-on’ clinical trial in mania showed ebselen’s superiority over placebo after three weeks of treatment. Our ongoing experimental research explores ebselen’s antidepressant profile in patients with treatment resistant depression. If successful, this will lead to a clinical trial of ebselen as an antidepressant augmentation agent, similar to lithium.

SeminarNeuroscience

Carnosine negatively modulates pro-oxidant activities of M1 peripheral macrophages and prevents neuroinflammation induced by amyloid-β in microglial cells

Giuseppe Caruso

Department of Drug Sciences, University of Catania

Oct 1, 2020

Carnosine is a natural dipeptide widely distributed in mammalian tissues and exists at particularly high concentrations in skeletal and cardiac muscles and brain. A growing body of evidence shows that carnosine is involved in many cellular defense mechanisms against oxidative stress, including inhibition of amyloid-β (Aβ) aggregation, modulation of nitric oxide (NO) metabolism, and scavenging both reactive nitrogen and oxygen species. Different types of cells are involved in the innate immune response, with macrophage cells representing those primarily activated, especially under different diseases characterized by oxidative stress and systemic inflammation such as depression and cardiovascular disorders. Microglia, the tissue-resident macrophages of the brain, are emerging as a central player in regulating key pathways in central nervous system inflammation; with specific regard to Alzheimer’s disease (AD) these cells exert a dual role: on one hand promoting the clearance of Aβ via phagocytosis, on the other hand increasing neuroinflammation through the secretion of inflammatory mediators and free radicals. The activity of carnosine was tested in an in vitro model of macrophage activation (M1) (RAW 264.7 cells stimulated with LPS + IFN-γ) and in a well-validated model of Aβ-induced neuroinflammation (BV-2 microglia treated with Aβ oligomers). An ample set of techniques/assays including MTT assay, trypan blue exclusion test, high performance liquid chromatography, high-throughput real-time PCR, western blot, atomic force microscopy, microchip electrophoresis coupled to laser-induced fluorescence, and ELISA aimed to evaluate the antioxidant and anti-inflammatory activities of carnosine was employed. In our experimental model of macrophage activation (M1), therapeutic concentrations of carnosine exerted the following effects: 1) an increased degradation rate of NO into its non-toxic end-products nitrite and nitrate; 2) the amelioration of the macrophage energy state, by restoring nucleoside triphosphates and counterbalancing the changes in ATP/ADP, NAD+/NADH and NADP+/NADPH ratio obtained by LPS + IFN-γ induction; 3) a reduced expression of pro-oxidant enzymes (NADPH oxidase, Cyclooxygenase-2) and of the lipid peroxidation product malondialdehyde; 4) the rescue of antioxidant enzymes expression (Glutathione peroxidase 1, Superoxide dismutase 2, Catalase); 5) an increased synthesis of transforming growth factor-β1 (TGF-β1) combined with the negative modulation of interleukines 1β and 6 (IL-1β and IL-6), and 6) the induction of nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1). In our experimental model of Aβ-induced neuroinflammation, carnosine: 1) prevented cell death in BV-2 cells challenged with Aβ oligomers; 2) lowered oxidative stress by decreasing the expression of inducible nitric oxide synthase and NADPH oxidase, and the concentrations of nitric oxide and superoxide anion; 3) decreased the secretion of pro-inflammatory cytokines such as IL-1β simultaneously rescuing IL-10 levels and increasing the expression and the release of TGF-β1; 4) prevented Aβ-induced neurodegeneration in primary mixed neuronal cultures challenged with Aβ oligomers and these neuroprotective effects was completely abolished by SB431542, a selective inhibitor of type-1 TGF-β receptor. Overall, our data suggest a novel multimodal mechanism of action of carnosine underlying its protective effects in macrophages and microglia and the therapeutic potential of this dipeptide in counteracting pro-oxidant and pro-inflammatory phenomena observed in different disorders characterized by elevated levels of oxidative stress and inflammation such as depression, cardiovascular disorders, and Alzheimer’s disease.

SeminarNeuroscience

Fluoxetine and vortioxetine reverse depressive-like phenotype and memory deficits induced by amyloid-β (1-42) oligomers in mice: implication of transforming growth factor-β1 and oxidative stress

Giuseppe Caruso

Department of Drug Sciences, University of Catania

Sep 28, 2020

A long-term treatment with antidepressants reduces the risk to develop AD and different second-generation antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are currently studied for their neuroprotective properties in AD. An impairment of neurotrophic factors signaling seems to be a common pathophysiological event in depression and AD. In particular a deficit of transforming growth factor-β1 (TGF-β1) and increased oxidative stress have been found both in depression and AD. In the present work the SSRI fluoxetine and the new multimodal antidepressant vortioxetine were tested for their ability to prevent memory deficits and depressive-like phenotype in a non-transgenic mouse model of AD (i.c.v. Aβ1-42 injection) by rescue of TGF-β1 signaling. The same drugs were also tested for their ability to modulate the expression of pro-oxidant genes as well as of genes related to the antioxidant machinery.

oxidative stress

Latest

Neuroinflammation in Epilepsy: what have we learned from human brain tissue specimens ?

Redox and mitochondrial dysregulation in epilepsy

Ebselen: a lithium-mimetic without lithium side-effects?

Carnosine negatively modulates pro-oxidant activities of M1 peripheral macrophages and prevents neuroinflammation induced by amyloid-β in microglial cells

Fluoxetine and vortioxetine reverse depressive-like phenotype and memory deficits induced by amyloid-β (1-42) oligomers in mice: implication of transforming growth factor-β1 and oxidative stress

ASTROCYTE-DERIVED EXTRACELLULAR MITOCHONDRIA MAY SUPPORT NEURONAL FUNCTION UNDER CHRONIC OXIDATIVE STRESS

SELENOPROTEIN T MIMETIC, PSELT, AMELIORATES BEHAVIORAL ALTERATIONS AND OXIDATIVE STRESS IN A PRENATAL VALPROIC ACID MOUSE MODEL OF AUTISM

OXIDATIVE STRESS IN THE PATHOGENESIS OF MEGALENCEPHALIC LEUKOENCEPHALOPATHY WITH SUBCORTICAL CYSTS (MLC): TOWARD THE IDENTIFICATION OF POSSIBLE THERAPEUTIC TARGETS

OXIDATIVE STRESS-INDUCED DOWNREGULATION OF EXTRACELLULAR MATRIX COMPONENTS AND RECEPTOR TYROSINE KINASES IN HUMAN NEUROBLASTOMA CELLS

EARLY-LIFE STRESS IMPAIRS AVERSIVE MEMORY EXTINCTION AND ELEVATES OXIDATIVE STRESS IN THE DORSAL HIPPOCAMPUS OF ADULT MALE AND FEMALE RATS

INTERPLAY OF THE CELLULAR REDOX COFACTORS GSH/GSSG, NADH/NAD<SUP>+</SUP> AND NADPH/NADP<SUP>+</SUP> DURING OXIDATIVE STRESS IN CULTURED PRIMARY RAT ASTROCYTES

ST-2657, A DUAL G9A/H3R MODULATOR, AMELIORATES BEHAVIORAL DEFICITS, OXIDATIVE STRESS AND NEUROINFLAMMATION AND RESTORES NEUROPLASTICITY IN BTBR MICE MODEL OF AUTISM

EXPOSURE TO THE ANTIOXIDANT FOLIUM ALLEVIATES OXIDATIVE STRESS IN A VALPROIC ACID-INDUCED ANIMAL MODEL OF AUTISM

LOSS OF DJ-1 AND PARKIN IN PARKINSON’S DISEASE OLIGODENDROCYTES INDUCES OXIDATIVE STRESS AND IMPAIRS DIFFERENTIATION AND MYELINATION

IMPACT OF SORL1 DEFICIENCY ON MITOCHONDRIAL DYNAMICS, CALCIUM HANDLING AND OXIDATIVE STRESS IN ALZHEIMER’S DISEASE

NEURONAL SECRETOME REMODELLING IN RESPONSE TO AGE-RELATED OXIDATIVE STRESS

CHARACTERIZATION OF THE MOLECULAR MECHANISMS LEADING TO ELAVL4/HUD ALTERED LEVELS IN OXIDATIVE STRESS CONDITIONS WITH POSSIBLE IMPLICATIONS FOR SPORADIC ALS

NEUROINFLAMMATION AND OXIDATIVE STRESS AS EARLY DETERMINANTS OF SYNAPTIC DYSFUNCTION AND COGNITIVE IMPAIRMENT IN MOUSE MODELS OF FAMILIAL AND SPORADIC ALZHEIMER’S DISEASE

ANTIEPILEPTOGENIC EFFECT OF CDDO-EA VIA DUAL MODULATION OF OXIDATIVE STRESS AND INFLAMMATION IN PRECLINICAL EPILEPSY MODELS

LOSS OF FMRP IS ASSOCIATED WITH INCREASED VULNERABILITY TO OXIDATIVE STRESS AND CELLULAR SENESCENCE IN THE MOUSE MODEL OF FRAGILE X SYNDROME

The protective actions of DHEA/S and BDNF against oxidative stress in an in vitro model of vascular dementia

Role of HSP70 protein in SH-SY5Y differentiation and protection from oxidative stress-dependent cell damage

Sex-dependent neurodevelopmental vulnerability in prenatally stressed mouse offspring is mediated by oxidative stress and placental immune activation

Understanding the altered brain metabolism and oxidative stress: Insights into metabolic syndrome and premature aging in a novel obese rodent model

Targeting oxidative stress and prolyl hydroxylase domain inhibition as neuroprotective strategies against hypoxia in isolated rat hippocampal slices

Aged microglia in Alzheimer’s disease display a senescent and pro-inflammatory profile associated with mitochondrial oxidative stress

Cellular response to oxidative stress and senescence in Fmr1 knockout mice modelling Fragile X Syndrome

Combined restraint stress and metal exposure paradigms in rats; cognitive assessment, brain oxidative stress, caspase-3 mediated responses, microglial activation, and myelin health

Cranial irradiation directed to the right hemisphere causes cognitive impairment in association with increased oxidative stress

Does sleep protect against oxidative stress?

Dual inhibition of ecto-5'-nucleotidase (CD73) and adenosine A2A receptor reduces neuroinflammation and oxidative stress in TNF, IL-1α, C1q-induced neurotoxic astrocytes

Evaluation of the effects of taurine treatment on apoptotic processes, miR-34a, oxidative stress, and inflammatory markers in intracerebroventricular Amyloid Beta 1-42 injected rats

The impact of sauerkraut brine on oxidative stress and inflammation in C57BL/6 mice

The interplay between mTORC2 and oxidative stress in neurotoxic models of neurodegeneration

The interplay between oxidative stress, mitochondrial dysfunction, and alteration of parvalbumin interneurons in postmortem brain of Alzheimer’s disease and mild cognitive impairment patients

Local and systemic effects: Intermittent theta burst stimulation ameliorates 6-OHDA-induced Parkinson's disease pathology by modulating purinergic signaling and oxidative stress

The modulation of p75 neurotrophin receptor reduces oxidative stress and inflammation in a cellular model of Rett syndrome

Multiparametric analysis of metabolic and oxidative stress on lipids and proteins in microarray printed astrocytic and neuronal lipid raft membranes

Pre- and post-treatment with apigenin attenuates status epilepticus-induced neuronal death by reducing oxidative stress and inflammation in the mouse brain

AβPP-induced UPR transcriptomic signature of glial cells to oxidative stress as an adaptive mechanism to preserve cell function and Survival

Autonomic Disbalance During Systemic Inflammation is Associated with Oxidative Stress Changes in Sepsis Survivor Rats

Reduced light exposure as a lifestyle measure for the alleviation of diabetes-induced anxiety – the link with oxidative stress

Cholesterol metabolism is modulated by NGF in an astrocyte-derived cell line and exhibits a neuroprotective role against oxidative stress

Cytoprotective effects of Cordycepin against oxidative stress-induced DNA damage and apoptosis in C6 glial cells

Does early postnatal methamphetamine administration along with altered environment affect neurotransmitter and oxidative stress levels in adolescence of laboratory rat?