Background: Aroclor 1254 (A1254) interferes with normal dendritic growth and plasticity in the developing rodent brain, but mechanism(s) mediating this effect have yet to be established. Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) enhance activity of ryanodine receptor (RyR) calcium ion (Ca2+) channels, which play a central role regulating spatiotemporal dynamics intracellular Ca2+ signaling. signaling is predominant factor shaping arbors, whether PCB potentiation RyR influences...

Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) promote dendritic growth in hippocampal neurons via ryanodine receptor (RyR)-dependent mechanisms; however, downstream signaling events that link enhanced RyR activity to are unknown. Activity-dependent growth, which is a critical determinant of neuronal connectivity the developing brain, mediated by calcium ion (Ca(2+))-dependent activation Ca(2+)/calmodulin kinase-I (CaMKI), triggers cAMP response element binding protein...

Axonal morphology is a critical determinant of neuronal connectivity, and perturbation the rate or extent axonal growth during development has been linked to neurobehavioral deficits in animal models humans. We previously demonstrated that organophosphorus pesticide (OP) chlorpyrifos (CPF) inhibits cultured neurons. In this study, we used zebrafish model determine whether CPF, its oxon metabolite (CPFO), excreted trichloro-2-pyridinol (TCPy) alter spatiotemporal patterns vivo. Static...

Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can trigger convulsions that progress to life-threatening status epilepticus. Survivors face long-term morbidity including mild-to-severe decline in memory. It is posited neuroinflammation plays a key role the pathogenesis of OP-induced neuropsychiatric deficits. Rigorous testing this hypothesis requires preclinical models recapitulate relevant phenotypic outcomes. Here, we describe rat model acute OP...

Neuregulin-1 (NRG-1) has been shown to act as a neuroprotectant in animal models of nerve agent intoxication and other acute brain injuries. We recently demonstrated that NRG-1 blocked delayed neuronal death rats intoxicated with the organophosphate (OP) neurotoxin diisopropylflurophosphate (DFP). It proposed inflammatory mediators are involved pathogenesis OP neurotoxin-mediated damage. examined influence on responses rat following DFP intoxication. Microglial activation was determined by...

Similar to organophosphate (OP) nerve agents, diisopropylfluorophosphate (DFP) rapidly and irreversibly inhibits acetylcholinesterase, leading convulsions that can progress status epilepticus (SE). However, in contrast the OP long-term consequences of DFP-induced SE are not well known. Thus, we characterized spatiotemporal profile neuropathology during first 2 months following acute DFP intoxication. Adult, male Sprague Dawley rats administered pyridostigmine bromide (0.1 mg/kg, im) 30 min...

The Rit GTPase is widely expressed in developing and adult nervous systems, our previous data with pheochromocytoma cells implicate signaling NGF-induced neurite outgrowth. In this study, we investigated a role for neuronal morphogenesis. Expression of dominant-negative (dn) mutant hippocampal neurons inhibited axonal growth but potentiated dendritic growth. Conversely, constitutively active (ca) promoted Dendritogenesis regulated differently sympathetic versus that require NGF bone...

Neurodevelopmental disorders (NDDs), including intellectual disability, attention deficit hyperactivity disorder (ADHD), and autism spectrum (ASD), are pervasive, lifelong for which pharmacological interventions not readily available. Substantial increases in the prevalence of NDDs over a relatively short period may be attributed solely to genetic factors and/or improved diagnostic criteria. There is now consensus that multiple loci combined with environmental risk during critical periods...

Tetramethylenedisulfotetramine (tetramine; TETS) is a potent convulsant poison that considered to be chemical threat agent. To provide basis for the investigation of antidotes TETS-induced seizures, we characterized activity TETS in mice and rats when administered by intraperitoneal, intravenous, oral, intraventricular routes as single acute dose with repeated sublethal doses. In mice, parenteral oral caused immobility, myoclonic body jerks, clonic seizures forelimbs and/or hindlimbs, tonic...

Acute intoxication with organophosphates (OPs) can trigger seizures that progress to status epilepticus, and survivors often exhibit chronic neuropathology, cognitive impairment, affective disorders, and/or electroencephalographic abnormalities. Understanding how acute injury transitions persistent neurological sequelae is critical developing medical countermeasures for mitigating damage following OP-induced seizures. Here, we used in vivo magnetic resonance imaging (MRI) monitor the...

Clinical and experimental observations suggest that statins may be useful for treating diseases presenting with predominant neurogenic inflammation, but the mechanism(s) mediating this potential therapeutic effect are poorly understood. In study, we tested hypothesis act directly on sensory neurons to decrease expression of proinflammatory neuropeptides trigger specifically calcitonin gene-related peptide (CGRP) substance P. Reverse transcriptase-polymerase chain reaction, radioimmunoassay,...

Clinical and experimental evidence suggest that statins decrease sympathetic activity, but whether peripheral mechanisms involving direct actions on post-ganglionic neurons contribute to this effect is not known. Because tonic activity of these directly correlated with the size their dendritic arbor, we tested hypothesis arborization in neurons. Oral administration atorvastatin (20 mg/kg/day for 7 days) significantly reduced vivo ganglia adult male rats. In cultured neurons, caused dendrite...

BackgroundRecent epidemiologic studies have identified organophosphorus pesticides (OPs) as environmental factors potentially contributing to the increase in asthma prevalence over last 25 years. In support of this hypothesis, we demonstrated that environmentally relevant concentrations OPs induce airway hyperreactivity guinea pigs.ObjectivesSensitization allergen is a significant factor asthma, and shown sensitization changes virus-induced from an eosinophil-independent mechanism one...

Background Epidemiological studies link organophosphorus pesticide (OP) exposures to asthma, and we have shown that the OPs chlorpyrifos, diazinon parathion cause airway hyperreactivity in guinea pigs 24 hr after a single subcutaneous injection. OP-induced involves M2 muscarinic receptor dysfunction on nerves independent of acetylcholinesterase (AChE) inhibition, but how inhibit neuronal receptors airways is not known. In central nervous system, interact directly with neurons alter function...

It has recently been reported that soluble epoxide hydrolase (sEH), the major enzyme metabolizes epoxyeicosatrienoic acids (EETs), is expressed in axons of cortical neurons; however, functional relevance axonal sEH localization unknown. Immunocytochemical analyses demonstrate predominant primary cultures not only but also sympathetic and sensory neurons. Morphometric cultured neurons indicate exposure to a regioisomeric mixture EETs (0.01-1.0 μM) causes concentration-dependent increase axon...

Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity, the OP parathion causes airway hyperreactivity guinea pigs as a result of functional loss inhibitory M2 muscarinic receptors on parasympathetic nerves. Because macrophages associated with asthma, we investigated whether mediate parathion-induced receptor dysfunction and hyperreactivity. Airway physiology was measured 24 h...