Abstract Inflammation is implicated in the progressive nature of neurodegenerative diseases, such as Parkinson's disease, but mechanisms are poorly understood. A single systemic lipopolysaccharide (LPS, 5 mg/kg, i.p.) or tumor necrosis factor alpha (TNFα, 0.25 injection was administered adult wild‐type mice and lacking TNFα receptors (TNF R1/R2 −/− ) to discern inflammation transfer from periphery brain consequences. Systemic LPS administration resulted rapid increase that remained elevated...

Parkinson's disease is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra. We have previously reported that lipopolysaccharide (LPS)-induced mediated release proinflammatory factors from activated microglia. Here, we report pivotal role NADPH oxidase inflammation-mediated neurotoxicity, where LPS-induced loss nigral vivo was significantly less pronounced oxidase-deficient (PHOX-/-) mice when compared with control (PHOX+/+) mice. Dopaminergic primary...

Abstract Background Cytokines and alcohol share a common modulation of inflammation hormones as well being implicated in multiple diseases, but the mechanisms are poorly understood. The purpose this study was to investigate interaction liver, serum brain cytokines whether ethanol would potentiate endotoxin (Lipopolysaccharide, LPS) responses once had cleared. Methods Male C57BL/6J mice were treated intragastrically with water (control) or (5 g/kg, i.g., 25% ethanol, w/v), volumes matched,...

Cytokines are multifunctional proteins that play a critical role in cellular communication and activation. have been classified as being proinflammatory (T helper 1, Th1) or anti‐inflammatory 2, Th2) depending on their effects the immune system. However, cytokines impact variety of tissues complex manner regulates inflammation, cell death, proliferation migration well healing mechanisms. Ethanol (alcohol) is known to alter cytokine levels including plasma, lung, liver, brain. Studies human...

The contributing role of environmental factors to the development Parkinson's disease has become increasingly evident. We report that mesencephalic neuron-glia cultures treated with diesel exhaust particles (DEP; 0.22 microM) (5-50 microg/ml) resulted in a dose-dependent decrease dopaminergic (DA) neurons, as determined by DA-uptake assay and tyrosine-hydroxylase immunocytochemistry (ICC). selective toxicity DEP for DA neurons was demonstrated lack effect on both GABA uptake Neu-N...

Activation of microglia causes the production proinflammatory factors and upregulation NADPH oxidase (NOX) that form reactive oxygen species (ROS) lead to neurodegeneration. Previously, we reported 10 daily doses ethanol treatment induced innate immune genes in brain. In present study, investigate effects chronic on activation NOX release ROS, their contribution neurotoxicity.Male C57BL/6 NF-κB enhanced GFP mice were treated intragastrically with water or (5 g/kg, i.g., 25% w/v) for days....

Parkinson's disease is characterized by a progressive degeneration of substantia nigra (SN) dopaminergic neurons with age. We previously found that single systemic lipopolysaccharide (LPS, 5 mg/kg, i.p.) injection caused slow loss tyrosine hydroxylase immunoreactive (TH+IR) in SN associated increasing motor dysfunction. In this study, we investigated the role NADPH oxidase (NOX) inflammation‐mediated neurotoxicity. A comparison control (NOX2 +/+ ) mice NOX subunit gp91 phox ‐deficient −/− 10...

The purpose of this study was to assess and compare the toxicity beta-amyloid (Abeta) on primary cortical mesencephalic neurons cultured with without microglia in order determine mechanism underlying microglia-mediated Abeta-induced neurotoxicity. Incubation or neuron-enriched mixed neuron-glia cultures Abeta(1-42) over concentration range 0.1-6.0 microm caused concentration-dependent High concentrations Abeta (6.0 for cortex 1.5-2.0 mesencephalon) directly injured cultures. In contrast,...

We determined the roles of reactive oxygen species (ROS) in expression cyclooxygenase-2 (COX-2) and production prostaglandin E2 (PGE2) lipopolysaccharide (LPS)-activated microglia. LPS treatment increased intracellular ROS rat microglia dose-dependently. Pre-treatment with superoxide dismutase (SOD)/catalase, or SOD/catalase mimetics that can scavenge ROS, significantly attenuated LPS-induced release PGE2. Diphenylene iodonium (DPI), a non-specific NADPH oxidase inhibitor, decreased PGE2...

Abstract Microglia are activated by lipopolysaccharide (LPS) to produce neurotoxic pro‐inflammatory factors and reactive oxygen species (ROS). While a multitude of LPS receptors corresponding pathways have been identified, the detailed mechanisms mediating microglial response unclear. Using mice lacking functional toll‐like receptor 4 (TLR4), we demonstrate that TLR4 ROS work in concert mediate microglia activation, where contribution from each pathway is dependent on concentration LPS....

Inflammation in the brain has increasingly been recognized to play an important role pathogenesis of several neurodegenerative disorders, including Parkinson9s disease and Alzheimer9s disease. Inflammation-mediated neurodegeneration involves activation brain9s resident immune cells, microglia, which produce proinflammatory neurotoxic factors, cytokines, reactive oxygen intermediates, nitric oxide, eicosanoids that impact on neurons induce neurodegeneration. Hence, identification compounds...

Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra and depletion neurotransmitter dopamine striatum. Progress search for effective therapeutic strategies that can halt this degenerative process remains limited. Mechanistic studies using animal systems such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent PD model have revealed involvement brain's immune cells free radical-generating...

Background: Binge ethanol administration causes corticolimbic brain damage that models alcoholic neurodegeneration. The mechanism of binge ethanol‐induced degeneration is unknown, but not simple glutamate– N ‐methyl‐ d ‐aspartate (NMDA) excitotoxicity. To test the hypothesis oxidative stress and inflammation are mechanisms damage, we administered 4 antioxidants, e.g., butylated hydroxytoluene (BHT), ebselen (Eb), vitamin E (VE), blueberry (BB) extract, during treatment assessed various...

Increasing evidence links systemic inflammation to neuroinflammation and neurodegeneration. We previously found that endotoxin, a TLR4 agonist or TNFα, increased blood TNFα entered the brain activating microglia persistent neuroinflammation. Further, we models of ethanol binge drinking sensitized proinflammatory responses. hypothesized cytokines contribute magnitude primes Here, investigate effects chronic on neurodegeneration triggered by toll-like receptor 3 (TLR3) poly...

The herbicide paraquat (PQ) has been implicated as a potential risk factor for the development of Parkinson's disease. In this study, PQ (0.5-1 microM) was shown to be selectively toxic dopaminergic (DA) neurons through activation microglial NADPH oxidase and generation superoxide. Neuron-glia cultures exposed exhibited decrease in DA uptake decline number tyrosine hydroxylase-immunoreactive cells. selectivity confirmed when failed alter gamma-aminobutyric acid neuron-glia cultures....

Unregulated microglial activation has been implicated as a pivotal factor contributing to Parkinson's disease. Using mesencephalic neuron-glia cultures, we address the novel possibility that peptides endogenous substantia nigra (SN), substance P and dynorphin (10(-13)-10(-14) M), are opposing mediators of consequent DA neurotoxicity. Here, identify M) is selectively toxic neurons in microglia-dependent manner. Mechanistically, activated NADPH oxidase produce extracellular superoxide...

Many brain disorders, including alcohol use disorder (AUD), are associated with induction of multiple proinflammatory genes. One aspect signaling is progressive increases in expression across cells and other innate immune High-mobility group box 1 (HMGB1) heteromers contribute to amplification by potentiating responses, Toll-like receptors (TLRs). TLR recruits coupling proteins linked nuclear transcription factors that induce cytokines chemokines their respective receptors. We tested the...

Although the cause of progressive neurodegeneration is often unclear, neuronal death can occur through several mechanisms. In conditions such as Alzheimer’s or alcohol use disorder (AUD), Toll-like receptor (TLR) induction observed with neurodegeneration. However, links between TLR activation and are lacking. We report a role apoptotic in AUD TLR7-mediated signaling. postmortem human cortex, two-fold increase terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining...

Previously we reported that naloxone stereoisomers, in an opioid receptor-independent manner, attenuated the inflammation-mediated degeneration of dopaminergic neurons by inhibition activation microglia, resident immune cells brain. Recently discovered β-amyloid peptide Aβ (1–42) exhibited enhanced neurotoxicity toward both cortical and mesencephalic through microglia production superoxide. The purpose this study was to determine whether isomers had any effect on (1–42)-induced...