Reactive oxygen species

Different brain cell types exhibit distinct metabolic signatures that link energy economy to cellular function. Astrocytes and neurons, for instance, diverge dramatically in their reliance on glycolysis versus oxidative phosphorylation, underscoring that metabolic fuel efficiency is not uniform across cell types. A key factor shaping this divergence is the structural organization of the mitochondrial respiratory chain into supercomplexes. Specifically, complexes I (CI) and III (CIII) form a CI–CIII supercomplex, but the degree of this assembly varies by cell type. In neurons, CI is predominant

…of polystyrene to benzophenone, where reactive oxygen species explain the observed chemistry rather than the previously proposed pathway. It also examines unwanted flavour changes in champagne, tracing a light-induced defect to a dimeric radical-cation intermediate. These cases connect mechanistic evidence with process optimization, industrial scale-up and possible chemical protection strategies.

…leads to a release of cytokines and reactive oxygen species followed by leakage of the blood-brain barrier and neurotoxicity. Transient neuroinflammation is understood to be largely protective, chronic neuroinflammation, however, contributes to the pathology of Alzheimer’s disease, traumatic brain injury, and many more. In this study, we focus on the aspect of cytokine-induced neuroinflammation in human microglia cells and especially in astrocytes, since many studies on

Alzheimer's disease (AD) is a progressive degenerative disorder characterized by memory loss and cognitive decline. However, there are limited studies on preventing or stopping the advanced neuronal loss that occurs during or before the disease. Our project aims to provide a prophylactic application against AD and similar neurodegenerative diseases. Exosomes are small particles that can cross biological membranes like the blood-brain barrier. They are being used as drug carrier systems and have attracted attention recently. In AD and similar diseases, exposure to oxidant molecules increases in

…Additionally, the effects on reactive oxygen species (ROS) generation (

Radiotherapy (RT) is the mainstay of brain cancer treatment due the generation of reactive oxygen species that cause double- and single-stranded DNA breaks. Although tumour cells are more radiosensitive, healthy cells are also subject to radiation damage, and as such therapeutic radiation can induce progressive cognitive decline. We investigated whether radiation-induced cognitive impairments could be prevented with the antioxidant tempol. Male C57BL/6 mice aged 27 weeks were administered either tempol (100mg/kg/day) or 0.9% saline for seven consecutive days via the I.P. route. One day after t

…Indeed, reactive oxygen species (ROS) have been shown to accumulate during prolonged waking, and experimentally increasing the ROS load of the brain induces sleep. In Drosophila melanogaster, a crucial ROS sensor in sleep-promoting dorsal fan-shaped body neurons (dFBNs) is the β-subunit, termed Hyperkinetic (Hk), of the voltage-gated potassium channel Shaker. Oxidation of a stably bound NADPH cofactor causes conformational changes in the channel, which increase dFBN activity. dFB

…damaging factors of the stroke is the reactive oxygen species generation occurring in mitochondrial respiratory chain (electron transport chain, ETC). We used in vivo Raman microspectroscopy with the chronic cranial windows implantation to assess the redox state of mitochondria ETC in neurons of awake mice under normal and hyperg

A growing body of evidence emphasizes that hypometabolism taking place in astrocytes may compromise their physiological neuro-supportive role and activate a set of pathophysiological pathways contributing to the progression of neurodegenerative diseases, including Alzheimer disease (AD) [1]. Here, we explored the potential role of astrocytes in driving a cascade of detrimental effects in the neighboring neurons and investigated a possible approach to limit the injury in both cell types [2]. To this aim, primary rat cortical astrocytes were exposed to glyceraldehyde (GA) to induce a metabolic s

Oxidative stress and neuroinflammation are crucial phenomena in the pathogenesis of Alzheimer disease (AD). Oxotremorine-M (Oxo), a non-selective muscarinic acetylcholine receptors agonist, exerts neurotrophic functions in primary neurons and modulates oxidative stress and neuroinflammation phenomena in rat brain. Based on this, our study investigates Oxo positive effects on differentiated SH-SY5Y neuroblastoma cells, revealing that Oxo treatment a) enhances cell survival, b) increases neurite length and c) upregulates HSP70 and pHSF1 expression. Moreover, Oxo counteracts tert–Butyl hydroperox

Physiological levels of reactive oxygen species (ROS) are required for the proper regulation of biological functions and cell signaling. However, ROS overproduction and inadequate scavenging lead to oxidative stress and consequent damage to macromolecules. Recent evidence has demonstrated the incontrovertible involvement of oxidative stress in the onset and progression of different central nervous system (CNS) disorders, including neurodegenerative events. For instance, redox disbalance together with α-synuclein aggregation and neuroinflammation, contributes to the loss of dopaminergic neurons

…exerts its cytotoxicity by generating reactive oxygen species (ROS) such as hydrogen peroxide, superoxide anion and hydroxyl-radical, leading to oxidative stress by disrupting the mitochondrial membrane integrity,

Reactive oxygen species (ROS) play a central role in enhancing inhibitory signal transmission, thus extending their role beyond oxidative stress in disease and aging. However, the underlying molecular mechanisms mediating these functions have remained elusive. At inhibitory synapses, the scaffolding protein gephyrin clusters glycine and GABA type A receptors. Since gephyrin harbors multiple surface-exposed cysteines, we investigated the regulatory influence of ROS on gephyrin. We show that H2O2-induced oxidation of gephyrin cysteines triggered reversible, synaptic multimerization through disul

…significantly ameliorated formation of reactive oxygen species and cell death in H

Parkinson's disease (PD), characterized by the absence of dopamine in the striatum[1], is caused by the death of the substantia nigra pars compacta dopamine (SNcDA) neurons in the mid-brain. The cause of this cell loss is attributed to irreparable damage due to a dysregulation cascade originating from excess cytosolic dopamine[2]. However, it is unresolved if dopamine dysregulation in SNcDA neurons themselves is the cause of PD or if it is a mere symptom. Here, we introduce a theory of specialized non-causal action potentials that serve metabolic homeostasis called `metabolic spikes' which can

…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 sho

Conventionally, neurons are thought to be cellular units that process synaptic inputs into synaptic spikes. However, it is well known that neurons can also spike spontaneously and display a rich repertoire of firing properties with no apparent functional relevance e.g. in in vitro cortical slice preparations. In this talk, I will propose a hypothesis according to which intrinsic excitability in neurons may be a survival mechanism to minimize toxic byproducts of the cell’s energy metabolism. In neurons, this toxicity can arise when mitochondrial ATP production stalls due to limited ADP. Under t

L-DOPA-induced dyskinesia is a debilitating adverse effect of treating Parkinson’s disease with this drug. New therapeutic approaches that prevent or attenuate this side effect is clearly needed. Wistar adult male rats submitted to 6-hydroxydopamine-induced unilateral medial forebrain bundle lesions were treated with L-DOPA (oral or subcutaneous, 20 mg kg-1) once a day for 14 days. After this period, we tested if doxycycline (40 mg kg-1, intraperitoneal, a subantimicrobial dose) and COL-3 (50 and 100 nmol, intracerebroventricular) could reverse LID. In an additional experiment, doxycycline was

Spontaneous firing, observed in many neurons, is often attributed to ion channel or network level noise. Cortical cells during slow wave sleep exhibit transitions between so called Up and Down states. In this sleep state, with limited sensory stimuli, neurons fire in the Up state. Spontaneous firing is also observed in slices of cholinergic interneurons, cerebellar Purkinje cells and even brainstem inspiratory neurons. In such in vitro preparations, where the functional relevance is long lost, neurons continue to display a rich repertoire of firing properties. It is perplexing that these neuro