Oxidative stress is implicated in neuronal apoptosis that occurs physiological settings and neurodegenerative disorders. Superoxide anion radical, produced during mitochondrial respiration, involved the generation of several potentially damaging reactive oxygen species including peroxynitrite. To examine directly role superoxide peroxynitrite apoptosis, we generated neural cell lines transgenic mice overexpress human manganese dismutase (MnSOD). In cultured pheochromocytoma PC6 cells,...

Oxidative stress is believed to play important roles in neuronal cell death associated with many different neurodegenerative conditions (e.g., Alzheimer's disease, Parkinson's and cerebral ischemia), it also that apoptosis an mode of these disorders. Membrane lipid peroxidation has been documented the brain regions affected disorders as well culture vivo models. We now provide evidence 4-hydroxynonenal (HNE), aldehydic product membrane peroxidation, a key mediator induced by oxidative...

Food restriction (FR) in rodents is known to extend life span, reduce the incidence of age-related tumors, and suppress oxidative damage proteins, lipids, DNA several organ systems. Excitotoxicity mitochondrial impairment are believed play major roles neuronal degeneration death that occurs brains patients suffering from both acute brain insults such as stroke seizures, chronic neurodegenerative conditions Alzheimer's, Parkinson's, Huntington's diseases. We now report FR (alternate-day...

J. Neurochem. (2012) 120 , 1060–1071. Abstract This study describes the effects of long‐chain fatty acids on inflammatory signaling in cultured astrocytes. Data show that saturated acid palmitic acid, as well lauric and stearic trigger release TNFα IL‐6 from Unsaturated were unable to induce cytokine Furthermore, require Toll‐like receptor 4 rather than CD36 or 2, do not depend metabolism palmitoyl‐CoA. Inhibitor studies revealed pharmacologic inhibition p38 p42/44 MAPK pathways prevents...

J. Neurochem. (2010) 114 , 1581–1589. Abstract Long term consumption of a high fat diet (HFD) contributes to increased morbidity and mortality. Yet the specific effects HFD on brain aging are poorly understood. In present study 20‐month old male C57Bl/6 mice were fed either ‘western diet’ (41% fat), very lard (60% or corresponding control diets for 16 weeks then assessed changes in metabolism homeostasis. Although both HFDs adiposity fasting blood glucose, only age‐related oxidative damage...

In the present study effects of 17β-estradiol on microglial activation are described. Estrogen replacement therapy has been associated with decreased severity age-related neurodegenerative diseases such as Alzheimer's disease, and estrogens have potent immunosuppressive properties outside brain. To determine role that cells might play in estrogen-mediated neuroprotection, primary rat microglia N9 cell lines were treated increasing doses before or during immunostimulation by...

Uric acid is a well-known natural antioxidant present in fluids and tissues throughout the body. Oxyradical production cellular calcium overload are believed to contribute damage death of neurons that occurs following cerebral ischemia victims stroke. We now report uric protects cultured rat hippocampal against cell induced by insults relevant pathogenesis ischemia, including exposure excitatory amino glutamate metabolic poison cyanide. Confocal laser scanning microscope analyses showed...

Tumor necrosis factor α (TNFα) is widely expressed in both neurons and glia has been shown to be upregulated after traumatic brain injury (TBI). TNFα receptor activation results of the transcription nuclear κB (NF-κB), which may serve an antiapoptotic role via induction target genes manganese superoxide dismutase (MnSOD) and/or calbindin. In present study, we used a controlled cortical impact model TBI with pertinent lines transgenic mice combine morphological characterization molecular...

Ischemic and excitotoxic insults to the brain induce rapid production of tumor necrosis factor-α (TNF), but role TNF in neuronal responses injury are unclear. Two different receptors (p55 p75) expressed neurons glia, To understand injury, we generated mice that lack p55, p75, or both receptors, We report damage after focal cerebral ischemia—reperfusion is significantly increased lacking p55 (85 ± 7 mm 3 infarct volume; mean SD) compared with wild-type (70 8 ) p75 (72 6 ). Moreover, exhibited...

Many cases of autosomal dominant early onset Alzheimer's disease (AD) result from mutations in the gene encoding presenilin-1 (PS-1). PS-1 is an integral membrane protein expressed ubiquitously neurons throughout brain which it located primarily endoplasmic reticulum (ER). Although pathogenic mechanism unknown, recent findings suggest that PS render vulnerable to apoptosis. Because increasing evidence indicates mitochondrial alterations contribute neuronal death AD, we tested hypothesis...

Abstract: We investigated the effect of uncoupling astrocytic gap junctions on neuronal vulnerability to oxidative injury in embryonic rat hippocampal cell cultures. Mixed cultures (neurons growing an astrocyte monolayer) treated with 18‐α‐glycyrrhetinic acid (GA), uncoupler junctions, showed markedly enhanced generation intracellular peroxides (2,7‐dichlorofluorescein fluorescence), impairment mitochondrial function [(dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide reduction], and...

Nuclear factor-κB (NF-κB) is activated in brain cells after various insults, including cerebral ischemia and epileptic seizures. Although cell culture studies have suggested that the activation of NF-κB can prevent neuronal apoptosis, role this transcription factor injury vivo unclear, specific κB subunits involved are unknown. We now report mice lacking p50 subunit exhibit increased damage to hippocampal pyramidal neurons administration excitotoxin kainate. Gel-shift analyses showed...

Inhibition of proteasome activity occurs in normal aging and a wide variety neurodegenerative conditions including Alzheimer's disease Parkinson's disease. Although each these is also associated with mitochondrial dysfunction potentially mediated by inhibition, the relationship between inhibition loss homeostasis has not been fully elucidated. In this study, we conducted experimentation order to begin develop more complete understanding effects on neural homeostasis. Mitochondria within...

The bcl-2 protooncogene product possesses antiapoptotic properties in neuronal and nonneuronal cells. Recent data suggest that Bcl-2's potency as a survival factor hinges on its ability to suppress oxidative stress, but neither the subcellular site(s) nor mechanism of action is known. In this report electron paramagnetic resonance (EPR) spectroscopy analyses were used investigate local effects Bcl-2 membrane lipid peroxidation. Using hydrogen peroxide (H2O2) amyloid beta-peptide (A beta)...

Abstract HIV encephalitis (HIVE) is accompanied by brain inflammation, leukocyte infiltration, and glial activation, patients who abuse opiates are more likely to develop HIVE. To better understand how could alter HIV‐related the expression of astrocyte (GFAP immunoreactivity) macrophage/microglial (F4/80 or Mac1 markers in striatum, percentage 3‐nitrotyrosine (3‐NT) positive macrophages/microglia, was determined following a 2‐day exposure morphine (5 mg/kg/day via time‐release, subcutaneous...

While considerable knowledge has been gained through the use of established cognitive and motor assessment tools, there is a interest need for development battery reliable validated tools that provide real-time remote analysis function in elderly. Smartphones appear to be an obvious choice these "next-generation" geriatric research, although date no studies have reported on smartphone-based applications study cognition The primary focus current was assess feasibility, reliability, validity...

The lateral hypothalamus (LHA) integrates reward and appetitive behavior is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHA<i>^GABA</i>), which densely innervate the ventral tegmental area (VTA), with modulation food consumption; yet, LHA<i>^GABA</i> projections to VTA exclusively modulated consumption, not reward. We identified a subpopulation that coexpress neuropeptide galanin (LHA<i>^Gal</i>). These...