The memory impairment in water-maze experiments, generally reported with BZ site agonists, was completely circumvented with all four ligands. The results suggest that a substantial amount of activity at a I GABA(A) receptors is needed for affecting spatial learning and memory impairments, while much weaker activity at alpha(1) and alpha(5)-GABA(A) receptors is sufficient for eliciting sedation. (C) 2010 Elsevier Inc. All rights reserved.”
“Thrombin plays important

roles in the pathology of intracerebral hemorrhage (ICH). The recruitment of activated microglia, accompanied by thrombin-induced phosphorylation of the mitogen-activated protein kinase (MARK) family, contributes to ICH-associated neuron loss. Here we investigated the possibility that sesamin, a lignan of sesame seed oil, is a natural candidate as an inhibitor of microglial activation and MAPK pathways under ICH insults. Sesamin (30-100 mu M) suppressed thrombin-induced nitric THZ1 oxide (NO) production by primary-cultured rat microglia via inhibition of inducible www.selleckchem.com/products/tubastatin-a.html NO synthase (iNOS) protein expression, independently of the antioxidative effect. Sesamin selectively inhibited p44/42 MARK phosphorylation in the MARK family (p38 and p44/42) involved in iNOS protein expression in primary-cultured rat microglia. An in vivo rat ICH model

was prepared by intrastriatal injection of 0.20 U collagenase type IV unilaterally. learn more ICH evoked the phosphorylation of p44/42 MARK, microglial proliferation with morphological change into the activated ameboid form, and neuron loss. The

phosphorylation of p44/42 MARK was inhibited by intracerebroventricular administration of 30-nmol sesamin. Sesamin prevented ICH-induced increase of microglial cells in the perihematomal area. Notably, ramified microglia, the resting morphology, were observed in brain sections of the animals administrated sesamin. Sesamin furthermore achieved neuroprotection in the perihematomal area but not in the hematomal center. These results suggest that sesamin is a promising natural product as a novel therapeutic strategy based on the regulation of microglial activities accompanied by the activated p44/42 MARK pathway in ICH. (C). 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Polymorphic multidrug resistant protein 1 (MDR1) transports drugs against a concentration gradient across the blood-brain barrier and reduces their accumulation in the brain. MDR1 may therefore influence antipsychotic brain availability contributing to inter-individual differences in treatment response and adverse effects, regardless of plasma concentrations. In the present study we investigated the influence of two common MDR1 polymorphisms on the improvement of psychopathological symptoms and occurrence of extrapyramidal side effects (EPS) in Slovenian schizophrenia patients acutely treated with risperidone.