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In addition to important regulatory roles in gene expression through RNA interference, it has recently been shown that microRNAs display immune stimulatory effects through direct interaction with receptors of innate immunity of the Toll-like receptor family, aggravating neuronal damage and tumour growth. Yet no evidence exists on consequences of microRNA(More)
Current evidence indicates that glutamate acting via the N-methyl-D-aspartate (NMDA) receptor/ion channel complex plays a major role in the neuronal degeneration associated with a variety of neurological disorders. In this report the role of glycine in NMDA neurotoxicity was examined. We demonstrate that NMDA-mediated neurotoxicity is markedly potentiated(More)
Basal levels of the metabolites of dopamine (DA) were reduced following the chronic administration of haloperidol. The ability of small doses (50 or 100 micrograms/kg) of apomorphine to reduce the concentrations of the metabolite of DA, homovanillic acid (HVA), was also enhanced following the chronic administration of haloperidol. In addition, the(More)
Seroquel and the atypical antipsychotic clozapine were compared using a number of biochemical measures in rats which are indicative of potential antipsychotic activity and possible extrapyramidal side effect liability. Both in vitro and in vivo, these compounds are low potency D-2 dopamine (DA) receptor antagonists and are relatively more potent 5-HT2(More)
Factors affecting dopamine (DA) synthesis in rat striatal synaptosomes were examined by measuring the conversion of [3H]tyrosine (Tyr) to [3H]DA. Any [3H]DA that was synthesized was extracted into a toluene-based scintillation cocktail and quantitated by liquid scintillation spectrometry. The extraction was facilitated using di-(2-ethylhexyl) phosphoric(More)
Activation of phosphoinositide metabolism is an early event in signal transduction for a number of neurotransmitters and hormones. In primary cultures of rat neurocortical cells, various excitatory amino acids stimulate inositol phosphate production with a rank order of potency of quisqualate greater than ibotenate greater than glutamate greater than(More)
N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) inactivates a variety of monoamine neurotransmitter receptors. In this report, protection against EEDQ-induced inactivation of D-1 and D-2 DA receptors by DA antagonists and agonists was used to obtain a measure of occupancy of these receptors in vivo by such drugs. Rats were pretreated with drugs and(More)
Tracazolate (ICI 136,753) 4-butylamine-1-ethyl-6-methyl-1H-pyrazolo[3,4]pyridine-5-carboxylic acid ethyl ester is a non-benzodiazepine with anxiolytic-like activity in animal models. In contrast to the benzodiazepines, it enhances [3H]flunitrazepam binding in rat synaptic membrane fragments. The enhancement is potential by chloride ion and is due to an(More)
Several new non-benzodiazepine anxiolytics are reported. These include tracazolate, zopiclone, CL218,872, CGS9896, buspirone, MK-801 and fenobam. A comparison of anticonflict effects and propensity to cause sedation and potentiate the actions of ethanol is given as well as their effects upon the binding of [3H]flunitrazepam in vitro. Their anxiolytic(More)
Tau protein is known to be present in the paired helical filaments (PHFs) of Alzheimer brains. This study investigated the fragments of tau protein that remain bound to pronase-treated PHFs and conditions that lead to the release of these tau fragments from the core structure of the PHF. Antibody 423 reacted with PHFs and with fetal rat tau but not with(More)