Oxidative stress

Microglial phenotype during Alzheimer’s Disease (AD) continuum is under debate. At early stages, a protective phenotype with the typical DAM profile would participate in plaque compaction and Aβ degradation. Instead, human AD microglia (HAM) show an enhance aged/degenerative profile, supporting a microglial dysfunction as a central mechanism in AD aetiology. Recent findings from our lab described that peri-plaque microglia are highly reliant on oxygen levels and mitochondrial integrity. Nevertheless, mitochondrial implication in aged microglia during the disease progression remains unclear. Th

The blood-brain barrier (BBB) separates the peripheral circulation from the brain. Brain endothelial cells (BECs) line the inner lumen of blood vessels in the brain and express tight junction proteins, that prevent the leakage of molecules between the cells into the brain, and efflux transporters that actively pump molecules out of the brain. As we age, the BBB becomes leaky and dysfunctional, leading to cerebrovascular diseases and dementia. We here investigated how BECs become senescent, a major feature of aging, and change their metabolic profile. First, we demonstrate that both the chemoth

…defined by severe neuroinflammation, oxidative stress, and age-related pathophysiological processes. The CAG-hACE2 transgenic mice were designed to express the human angiotensin-converting enzyme 2 (hACE2) receptor, which is involved in the RAS. However, the relevance of ACE2 at the brain level remains unclear. The purpose of our research is to characterize CAG-hACE2 transgenic mice of both sexes, females an

…damage response and is a component of stress granules (SGs), cytoplasmatic aggregates that form in response to stress and are protective against apoptosis. Evidence in the mouse model of FXS suggests an excess of oxidizing

Voltage-gated potassium (Kv) channels couple with cytoplasmic ß-subunits (Kvß) that exhibit aldo-keto reductase (AKR) activity. Kvß subunits typically have exceptionally low catalytic turnover making them slow substrate converters. This poses a conundrum: why would an ion channel be shackled with a subpar enzyme? The AKR activity is crucial in Drosophila sleep regulation in dorsal fan-shaped body neurons (dFBN) where the Kv1 family member, Shaker, is paired with the ß-subunit Hyperkinetic. We show that its low catalytic turnover permits Hyperkinetic to monitor and integrate cumulative oxidativ

…Accumulating evidence suggests that oxidative stress plays a critical role in the development of epilepsy, and that pharmacological targeting of oxidative stress can prevent spontaneous seizures. However, non-specific antioxidant therapies may disrupt the physiological balance of oxidants/antioxidants, highlighting the need for targeted intervention. Here, we used AAV

Accumulation of heavy metals (Mn and Ni) and prolonged exposure to stress are associated with adverse health outcomes. Various studies have elucidated individually the impacts of stress and metal exposures on brain constituents and function. However, no study has examined the effects of co-exposure to stress, Mn, and Ni in the brain. This study addresses this gap by evaluating oxidative and glial responses, apoptotic activity, as well as cognitive processes in a rat model. Adult Wistar rats were exposed to vehicle (control), restraint stress, 25mg/kg of manganese (Mn) or nickel (Ni), and combi

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

Hypoxic injury in developing glial cells and their differential response can result in neurological deficits in neonates. This study attempts to understand the role of autophagy in developing premyelinating oligodendrocytes (pre-OL), mature-OL and astrocytes exposed to hypoxic injury. Human fetal neural stem cell-derived pre-OL, mature OL and astrocytes were exposed to hypoxia (0.2% oxygen) and normoxia (20% oxygen) for 48 hours followed by RNA-sequencing. Transcriptomic analysis revealed upregulation of autophagy in mature OL and astrocytes but not in pre-OL. MO3.13 (resembling pre-OL) and SV

Ecto-5'-nucleotidase (CD73) is an ecto-enzyme that hydrolyzes adenosine monophosphate to adenosine, which acts through one of four subtypes of adenosine receptors. Increased CD73 activity and expression in chronic neurodegenerative diseases leads to a higher concentration of adenosine in the extracellular space. This results in excessive activation of adenosine A2AR, which triggers proinflammatory signaling pathways that further promote neurodegeneration. Therefore, dual CD73/A2AR inhibition is a potential pharmacologic target in chronic neurodegeneration. In the present study, we used a novel

…There is evidence which suggests that oxidative stress has a key role in the pathogenesis of diabetes and its complications. Autophagy is one of the main routes to eliminate damaged components in cells in response to oxidative stress. However, excessive autophagy causes a distinct type of cell death involved in the pathogenesis of multiple diseases, such as diabetes. This study aimed to investigate the effect of melatonin on the autophagy in the pre

Recent studies have highlighted the pivotal role of TRPM2 channel activation in neurological disorders. Nevertheless, its association with epileptic seizures and subsequent neuronal damage remains unclear. This study aims to investigate the impact of inhibiting TRPM2 on 4-AP-induced seizures in mouse brain slices and the resultant neuronal damage in the HT-22 cell line. Electrophysiologically using LFP records the effect of TRPM2 inhibition through the TRPM2 antagonist N-ACA was demonstrated in the entorhinal cortex region after the 4-AP-induced seizure model. Furthermore, to shed light on the

Metal exposure is an intriguing potential culprit in the cause of sporadic amyotrophic lateral sclerosis (ALS). Lead (Pb), mercury (Hg), cadmium (Cd) and arsenic (As) are singled out among the ten chemicals of major public health concern by the World Health Organisation. There are numerous case reports and case-control studies linking those metals to an ALS phenotype. Additionally, some studies have demonstrated higher levels of these metals in the blood, cerebrospinal fluid, urine, or spinal cords of patients with ALS compared to controls. Recently, it has been proposed that the interaction b

…in the brain, accompanied by oxidative stress and a concurrent impact on cognitive function. The aim of this study is to evaluate the behavioral results of once or twice injections of the ICV STZ administration methods. ICV guide cannulas were placed unil

…the effects of ibrutinib on oxidative stress and inflammation in mouse microglial C8-B4 cell line, cells were treated with ibrutinib (1 and 10 μM) or vehicle (1% DMSO) for 1 h, followed by 1 μg/ml LPS or PBS in case of the control samples, for 23 h. Intracellular ROS was measured by using fluorescence microscopy using 2′,7′-dihydrofluorescein diacetate dye (DCFH-DA). Inflammatory mediator levels (NF kappa beta, TLR4, TNFalpha), and anti-inflammatory c

…ubiquitination dysregulation, and oxidative stress. Nicotine, found in tobacco, has been associated with reduced PD risk in epidemiological studies and shown neuroprotective effects in animal models. However, its impact on oxidative stress remains unclear. A study in

Extracellular vesicles (EVs) are membrane-enveloped nanoparticles released into the extracellular space by almost all cell types. They have been shown to spread α-synuclein (αSyn) – the main pathological hallmark of Parkinson´s disease (PD) – and miRNAs that can influence the expression of genes associated with PD progression. On this basis, they are becoming interesting as diagnostic biomarkers. So far, however, data from patients are heterogeneous and inconsistent. Therefore, we aim to use a cellular model that allows us to investigate the role of EVs in PD pathology on a homogeneous genetic

…mitochondrial alterations that lead to oxidative stress. Currently, the only treatment for PD patients is dopamine replacement therapy (levodopa), which has serious side effects and does

The oxidative stress and inflammation provoked by hypoxia can lead to damage to neurons in the hippocampus, a structure that plays a key role in learning and memory processes. Prevention of hypoxia-related damages may be achieved through different means: pharmacologically or behaviorally. Some plants have strong antioxidants properties, such as Guiera senegalensis (GS). Alternatively, performance of free-divers, without memory loss, suggests neuroprotective effects of extended training to apnea. We developed a rat model of hypoxia under voluntary apnea. Training consists of 3 to 4 weeks of hab

The effect of living conditions on the physiology, behaviour and stress of laboratory animals is still being discussed. There are conflicting findings regarding individually ventilated cages(IVC). This study aims to explore the effects of three distinct cage setups and to examine the differences in the impacts of IVC cages, classical cages and classical cages with varying mouse populations. Thirty male C57BL/6J strain mice were split into three groups:IVC, classical small(CC500) and big(CC800) with a floor size of 500 and 800 cm2,respectively. From birth until six months of age, the mice were

…several genes and proteins related to oxidative stress, such as Sod1, Gnao1, Stx4, Hmox2, Srxn1, and Edn1. The responses to oxid

Systemic inflammation, often triggered by structural components of gut bacteria such as lipopolysaccharide (LPS), triggers inflammatory processes involving cytokines and other pro-inflammatory molecules. These signaling pathways can be modulated by dietary measures, with fermented foods having anti-inflammatory and immunomodulatory functions. In this study, the effect of sauerkraut brine on lipopolysaccharide (LPS)-induced inflammation in C57BL/6 mice was investigated. Two experiments were performed when the animals were 91 days old. In the first experiment, the animals were divided into three

Aging is a multifactorial process characterized by the slow decline of cellular physiology associated with a lowdown of brain functions. Neurological complications mainly reflect defects at the synaptic structure. Indeed, preclinical studies demonstrate that preserving functionality of synapses delays the occurrence of aged-related neurological and cognitive defects and prevents the progressive neuronal degeneration. Since defects in DNA repair mechanisms have a critical role in aged-related neurological diseases and expression of core DNA repair genes is downregulated during aging across brai

…PVI are highly sensitive to oxidative stress (OS) and mitochondrial impairment, conditions that are well known to increase with ageing. Therefore, there is a critical n