okadaic-acid and Brain-Injuries

To study the effect of flavonoids isolated from aerial parts of Scutellaria baicalensis Georgi (SSF) on cerebral damage induced by okadaic acid (OA) in rats.. OA was microinjected into the right lateral ventricle of male rats at a dose of 200 ng kg(-1) twice with a 3-day interval between injections to establish a model of Alzheimer's-disease-like cerebral damage. Neuronal morphology was observed with thionin staining and the expressions of glial fibrillary acidic protein (GFAP) and β-amyloid peptide 1-40 (Aβ1-40) were monitored via immunohistochemistry. The level of malondialdehyde (MDA) and the activities of glutathione peroxidase (GSH-Px) and lactate dehydrogenase (LDH) were measured using spectrophotometry.. The results showed that OA-treated rats exhibited marked neuronal damage accompanied by increased levels of Aβ1-40 peptide and MDA accumulation, decreased GFAP protein expression and reduced GSH-Px and LDH activity in the brain. SSF at three doses (25, 50 and 100 mg kg(-1)) dramatically reversed the OA-induced changes in the brains of rats.. SSF-mediated amelioration of OA-induced neuronal damage in rats provides a rationale for assessing SSF as a means of to reducing tau hyperphosphorylation and Aβ expression in the treatment of Alzheimer's disease.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain Injuries; Disease Models, Animal; Flavonoids; Glial Fibrillary Acidic Protein; Glutathione Peroxidase; Immunohistochemistry; Injections, Intraventricular; L-Lactate Dehydrogenase; Lateral Ventricles; Male; Malondialdehyde; Microinjections; Neurons; Okadaic Acid; Oxidative Stress; Peptide Fragments; Random Allocation; Rats; Rats, Sprague-Dawley; Scutellaria baicalensis

Alzheimer's disease (AD) is histopathologically characterised by the formation of neurofibrillary tangles (NFTs) that are largely composed of hyperphosphorylated tau protein (PHF-tau), and senile plaques which contain aggregates of the Abeta peptide. Formation of PHF-tau and amyloidogenic processing of the amyloid precursor protein (APP) might be related to a disturbance in the balance between protein phosphorylation and dephosphorylation. In the present study, the effects of injections into the cerebral cortex of either okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, or saline were investigated. Both kinds of injections induced a reversible phosphorylation of tau, albeit to a different extent. The secretion of soluble APP was reduced after OA but not affected after injection of saline. It is concluded that phosphorylation of tau, similar though not identical to those seen in AD can be induced in vivo by inhibition of protein dephosphorylation as well as by unspecific lesion of cortical neurones. It might, therefore, be suggested that phosphorylation processes involved in PHF-formation in AD similarly reflect a neuronal response to injury.

Topics: Animals; Blotting, Western; Brain; Brain Chemistry; Brain Injuries; Electrophoresis, Polyacrylamide Gel; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; Male; Okadaic Acid; Phosphoprotein Phosphatases; Phosphorylation; Rats; Rats, Wistar; tau Proteins