DFP initiated early alterations of PKA/p-CREB pathway and differential persistence of beta-tubulin subtypes in the CNS of hens contributes to OPIDN.

Organophosphorus ester-induced delayed neurotoxicity (OPIDN) is a neurodegenerative disorder characterized by ataxia progressing to paralysis with a concomitant central and peripheral distal axonapathy. Diisopropylphosphorofluoridate (DFP) produces OPIDN in the chicken, which results in mild ataxia in 7-14 days and severe paralysis as the disease progresses with a single dose. White leghorn layer hens were treated with DFP (1.

Therapeutic targets in focal and segmental glomerulosclerosis.

Purpose Of Review: Focal and segmental glomerulosclerosis occurs due to a defect in the glomerular filtration barrier. This review highlights contributions from the past year that have enhanced our understanding of the pathophysiology of focal and segmental glomerulosclerosis with emphasis on discoveries which may lead to the identification of therapeutic targets.

Recent Findings: Slit diaphragm proteins have become increasingly important in signal transduction and in mediating downstream events.

TRPC6 and FSGS: the latest TRP channelopathy.

Focal and segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome in children and adults throughout the world. In the past 50 years, significant advances have been made in the identification and characterization of familial forms of nephrotic syndrome and FSGS. Resultant to these pursuits, several podocyte structural proteins such as nephrin, podocin, alpha-actinin 4 (ACTN4), and CD2-associated protein (CD2AP) have emerged to provide critical insight into the pathogenesis of hereditary nephrotic syndromes.

Toxicogenomic studies of the rat brain at an early time point following acute sarin exposure.

We have studied sarin-induced global gene expression patterns at an early time point (2 h: 0.5 x LD50) using Affymetrix Rat Neurobiology U34 chips and male Sprague-Dawley rats. A total of 46 genes showed statistically significant alterations from control levels.

Gene expression profiles of the rat brain both immediately and 3 months following acute sarin exposure.

We have studied sarin-induced global gene expression patterns at an early time point (15 min; 0.5xLD50) and a later time point (3 months; 1xLD50) using Affymetrix: Rat Neurobiology U34 chips in male, Sprague-Dawley rats and have identified a total of 65 (early) and 38 (late) genes showing statistically significant alterations from control levels at 15 min and 3 months, respectively. At the early time point, those that are classified as ion channel, cytoskeletal and cell adhesion molecules, in addition to neuropeptides and their receptors predominated over all other groups.

Sarin (nerve agent GB)-induced differential expression of mRNA coding for the acetylcholinesterase gene in the rat central nervous system.

We carried out a time-course study on the effects of a single intramuscular (i.m.) dose (0.

Early differential elevation and persistence of phosphorylated cAMP-response element binding protein (p-CREB) in the central nervous system of hens treated with diisopropyl phosphorofluoridate, an OPIDN-causing compound.

Diisopropyl phosphorofluoridate (DFP) produces organophosphorus-ester-induced delayed neurotoxicity in sensitive species. We studied the effect of single dose of DFP on the expression of phosphorylated cAMP-response element binding protein (p-CREB), which is a well known transcription factor involved in several pathways mediating different types of external stimuli. The hens were perfused with neutral buffered formalin at different time points, i.

Sarin causes altered time course of mRNA expression of alpha tubulin in the central nervous system of rats.

Sarin induced neurotoxicity is suspected to be one of the key factors responsible for Gulf-war syndrome. We studied the effect of a single (50 microg/kg/i.m) dose of sarin (0.

Differential alteration of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in the central nervous system of hens treated with diisopropylphosphorofluoridate (DFP).

A single dose (1.7 mg/kg, s.c.