Serotonin Depletion Does not Modify the Short-Term Brain Hypometabolism and Hippocampal Neurodegeneration Induced by the Lithium-Pilocarpine Model of Status Epilepticus in Rats.

It has been reported that fluoxetine, a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, has neuroprotective properties in the lithium-pilocarpine model of status epilepticus (SE) in rats. The aim of the present study was to investigate the effect of 5-HT depletion by short-term administration of p-chlorophenylalanine (PCPA), a specific tryptophan hydroxylase inhibitor, on the brain hypometabolism and neurodegeneration induced in the acute phase of this SE model. Our results show that 5-HT depletion did modify neither the brain basal metabolic activity nor the lithium-pilocarpine-induced hypometabolism when evaluated 3 days after the insult.

Subacute administration of fluoxetine prevents short-term brain hypometabolism and reduces brain damage markers induced by the lithium-pilocarpine model of epilepsy in rats.

The role of serotonin (5-hydroxytryptamine; 5-HT) in epileptogenesis still remains controversial. In this regard, it has been reported that serotonergic drugs can alter epileptogenesis in opposite ways. The main objective of this work was to investigate the effect of the selective 5-HT selective reuptake inhibitor (SSRI) fluoxetine administered subacutely (10mg/kg/day×7 days) on the eventual metabolic impairment induced by the lithium-pilocarpine model of epilepsy in rats.

Longitudinal assessment of a transgenic animal model of tauopathy by FDG-PET imaging.

Abnormal levels and hyperphosphorylation of tau protein have been proposed as the underlying cause of a group of neurodegenerative disorders collectively known as 'tauopathies'. The detrimental consequence is the loss of affinity between this protein and the microtubules, increased production of fibrillary aggregates, and the accumulation of insoluble intracellular neurofibrillary tangles. A similar phenotype can be observed in various preclinical models, which have been generated to study the role of tau protein in neurodegenerative disorders.

A longitudinal FDG-PET study of transgenic mice overexpressing GSK- 3β in the brain.

Increased Glycogen synthase kinase-3 (GSK-3) activity is believed to contribute to the etiology of chronic disorders such as Alzheimer's disease, one of the earliest diseases linked to GSK-3 dysfunction. Numerous mouse models with modified GSK-3 have been generated in order to study the physiology of GSK-3, its implication in diverse pathologies and the potential effect of GSK-3 inhibitors. In this study we have characterised and evaluated the brain metabolic changes induced by GSK-3β overexpression in transgenic mice throughout their lifespan.

Tau-knockout mice show reduced GSK3-induced hippocampal degeneration and learning deficits.

It has been proposed that deregulation of neuronal glycogen synthase kinase 3 (GSK3) activity may be a key feature in Alzheimer disease pathogenesis. We have previously generated transgenic mice that overexpress GSK3beta in forebrain regions including dentate gyrus (DG), a region involved in learning and memory acquisition. We have found that GSK3 overexpression results in DG degeneration.

Inhibition of glutamate release by delaying ATP fall accounts for neuroprotective effects of antioxidants in experimental stroke.

Excitotoxic neuronal injury related to excessive glutamate release is believed to play a key role in the pathogenesis of focal cerebral ischemia. Reversal of neuronal glutamate transporters caused by ATP fall and subsequent imbalance of membrane ionic gradients accounts for most glutamate release after cerebral ischemia. ATP synthesis from oxidative phosphorylation derives from the coupled functioning of the mitochondrial respiratory chain (MRC) and the ATP synthase; interestingly, the MRC is one of the main sites of cellular reactive oxygen species (ROS) generation even in physiological circumstances.

Aspirin inhibits stress-induced increase in plasma glutamate, brain oxidative damage and ATP fall in rats.

The precise mechanisms by which stress induces brain damage are still being elucidated. The high-output, inducible isoform of nitric oxide (NO) synthase (iNOS) is expressed in rat brain after immobilisation stress and its inhibition protects against cell damage in this condition. We have hereby explored some mechanisms involved in iNOS expression and studied the effects of aspirin, a NSAID with neuroprotective actions, in this model.

Inhibition of glutamate release via recovery of ATP levels accounts for a neuroprotective effect of aspirin in rat cortical neurons exposed to oxygen-glucose deprivation.

Background And Purpose: Aspirin is preventive against stroke not only because of its antithrombotic properties but also by other direct effects. The aim of this study was to elucidate its direct neuroprotective effects.

Methods: Viability parameters, glutamate release and uptake, and ATP levels were measured in cultured cortical neurons exposed to oxygen-glucose deprivation (OGD).