Acute intoxication with diisopropylfluorophosphate promotes cellular senescence in the adult male rat brain.

Acute intoxication with high levels of organophosphate (OP) cholinesterase inhibitors can cause cholinergic crisis, which is associated with acute, life-threatening parasympathomimetic symptoms, respiratory depression and seizures that can rapidly progress to status epilepticus (SE). Clinical and experimental data demonstrate that individuals who survive these acute neurotoxic effects often develop significant chronic morbidity, including behavioral deficits. The pathogenic mechanism(s) that link acute OP intoxication to chronic neurological deficits remain speculative.

Oxidized linoleic acid metabolites regulate neuronal morphogenesis in vitro.

Linoleic acid (LA, 18:2n-6) is an essential nutrient for optimal infant growth and brain development. The effects of LA in the brain are thought to be mediated by oxygenated metabolites of LA known as oxidized LA metabolites (OXLAMs), but evidence is lacking to directly support this hypothesis. This study investigated whether OXLAMs modulate key neurodevelopmental processes including axon outgrowth, dendritic arborization, cell viability and synaptic connectivity.

Transient Stimulation with Psychoplastogens Is Sufficient to Initiate Neuronal Growth.

Cortical neuron atrophy is a hallmark of depression and includes neurite retraction, dendritic spine loss, and decreased synaptic density. Psychoplastogens, small molecules capable of rapidly promoting cortical neuron growth, have been hypothesized to produce long-lasting positive effects on behavior by rectifying these deleterious structural and functional changes. Here we demonstrate that ketamine and LSD, psychoplastogens from two structurally distinct chemical classes, promote sustained growth of cortical neurons after only short periods of stimulation.

Organophosphorus Pesticides Induce Cytokine Release from Differentiated Human THP1 Cells.

Epidemiologic studies link organophosphorus pesticides (OPs) to increased incidence of asthma. In guinea pigs, OP-induced airway hyperreactivity requires macrophages and TNF-α. Here, we determined whether OPs interact directly with macrophages to alter cytokine expression or release.

A novel carboline derivative inhibits nitric oxide formation in macrophages independent of effects on tumor necrosis factor α and interleukin-1β expression.

Neuropathic pain is a maladaptive immune response to peripheral nerve injury that causes a chronic painful condition refractory to most analgesics. Nitric oxide (NO), which is produced by nitric oxide synthases (NOSs), has been implicated as a key factor in the pathogenesis of neuropathic pain. β-Carbolines are a large group of natural and synthetic indole alkaloids, some of which block activation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), a predominant transcriptional regulator of NOS expression.

Oxygen tension modulates differentiation and primary macrophage functions in the human monocytic THP-1 cell line.

The human THP-1 cell line is widely used as an in vitro model system for studying macrophage differentiation and function. Conventional culture conditions for these cells consist of ambient oxygen pressure (∼20% v/v) and medium supplemented with the thiol 2-mercaptoethanol (2-ME) and serum. In consideration of the redox activities of O₂ and 2-ME, and the extensive experimental evidence supporting a role for reactive oxygen species (ROS) in the differentiation and function of macrophages, we addressed the question of whether culturing THP-1 cells under a more physiologically relevant oxygen tension (5% O₂) in the absence of 2-ME and serum would alter THP-1 cell physiology.

IFNγ Increases M2 Muscarinic Receptor Expression in Cultured Sympathetic Neurons.

M2 muscarinic receptors are expressed on both parasympathetic and sympathetic nerve endings where they function as autoinhibitory receptors to limit release of acetylcholine and norepinephrine, respectively. M2 muscarinic receptor expression on parasympathetic nerves is decreased by viral infection and by gamma-interferon (IFNγ) and increased by dexamethasone; and these effects are of clinical relevance in the etiology and treatment of asthma. Whether IFNγ and dexamethasone similarly modulate M2 receptor expression on sympathetic nerves is not known.

Mast cell repopulation of the peritoneal cavity: contribution of mast cell progenitors versus bone marrow derived committed mast cell precursors.

Background: Mast cells have recently gained new importance as immunoregulatory cells that are involved in numerous pathological processes. One result of these processes is an increase in mast cell numbers at peripheral sites. This study was undertaken to determine the mast cell response in the peritoneal cavity and bone marrow during repopulation of the peritoneal cavity in rats.

FcepsilonRI-induced activation by low antigen concentrations results in nuclear signals in the absence of degranulation.

High affinity IgE receptor (FcvarepsilonRI)-induced activation of mast cells results in degranulation and generation of leukotrienes and cytokines. FcvarepsilonRI-induced mast cell activation was analyzed at a single cell basis using a rat basophilic leukemia (RBL-2H3) cell line transfected with a reporter plasmid containing three tandem NFAT (nuclear factor of activated T cells) binding sites fused to enhanced green fluorescent protein (GFP). Surprisingly, with this sensitive detection system, there is activation of IgE sensitized cells at concentrations of antigen as low as 10pg/ml, which was 10-fold lower than was detected by degranulation.

The low affinity IgG receptor Fc gamma RIIB contributes to the binding of the mast cell specific antibody, mAb BGD6.

The mast cell specific monoclonal antibody, mAb BGD6, is a mast cell lineage marker [Jamur, M.C., Grodzki, A.

Identification and characterization of undifferentiated mast cells in mouse bone marrow.

Sequential immunomagnetic isolation with 2 monoclonal antibodies was used to purify and characterize an undifferentiated mast cell in adult mouse bone marrow that had not been previously recognized. This cell represents 0.02% of the cells in the bone marrow, is CD34(+), CD13(+), and c-kit(+), and does not express FcepsilonRI.

Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation.

To investigate the role of phospholipase D (PLD) in FcepsilonRI signaling, the wild-type or the catalytically inactive forms of PLD1 or PLD2 were stably overexpressed in RBL-2H3 mast cells. FcepsilonRI stimulation resulted in the activation of both PLD1 and PLD2. However, PLD1 was the source of most of the receptor-induced PLD activity.