CNS-selective noncompetitive cholinesterase inhibitors derived from the natural piperidine alkaloid (-)-spectaline

LASSBio-767 [(-)-3-O-acetyl-spectaline] and LASSBio-822 [(-)-3-O-tert-Boc-spectaline] were recently described as cholinesterase inhibitors derived from the natural piperidine alkaloid (-)-spectaline, obtained from the flowers of Senna spectabilis (Fabaccae). We investigated their mechanism of inhibition of acetylcholinesterase and their efficacy in reversing scopolamine-induced amnesia. Competition assays with the substrate acetylthiocholine showed a concentration-dependent reduction in rat brain cholinesterase V-max without changes in apparent K-m. The kinetic data for LASSBio-767 and LASSBio-822 were best fit by a model of simple linear noncompetitive inhibition with K-i of 6.1 mu M and 7.5 mu M, respectively. A dilution assay showed a fast and complete reversal of inhibition, independent of incubation time. Simulated docking of the compounds into the catalytic gorge of Torpedo acetylcholinesterase showed interactions with the peripheral anionic site, but not with the catalytic triad. Anti-amnestic effects in mice were assessed in a step-down passive avoidance test and in the Morris water maze 30 min after injection of scopolamine (1 mg/kg i.p.). Saline, LASSBio-767, or LASSBio-822 was administered 15 min before scopolamine. Both compounds reversed the scopolamine-induced reduction in step-down latency at 0.1 mg/kg i.p. LASSBio-767 reversed scopolamine-induced changes in water maze escape latency at 1 mg/kg i.p. or p.o., while its cholinergic side effects were absent or mild up to 30 mg/kg i.p. (LD50 above 100 mg/kg i.p.). Thus, the (-)-spectaline derivatives are potent cholinergic agents in vivo, with a unique profile combining noncompetitive cholinesterase inhibition and CNS selectivity, with few peripheral side effects. (C) 2007 Elsevier B.V. All rights reserved.

Gestational protein restriction induces CA3 dendritic atrophy in dorsal hippocampal neurons but does not alter learning and memory performance in adult offspring

Studies have demonstrated that nutrient deficiency during pregnancy or in early postnatal life results in structural abnormalities in the offspring hippocampus and in cognitive impairment. In an attempt to analyze whether gestational protein restriction might induce learning and memory impairments associated with structural changes in the hippocampus, we carried out a detailed morphometric analysis of the hippocampus of male adult rats together with the behavioral characterization of these animals in the Morris water maze (MWM). Our results demonstrate that gestational protein restriction leads to a decrease in total basal dendritic length and in the number of intersections of CA3 pyramidal neurons whereas the cytoarchitecture of CA1 and dentate gyrus remained unchanged. Despite presenting significant structural rearrangements, we did not observe impairments in the MWM test. Considering the clear dissociation between the behavioral profile and the hippocampus neuronal changes, the functional significance of dendritic remodeling in fetal processing remains undisclosed. © 2012 ISDN.

Avaliação toxicológica da Ipomoea asarifolia (salsa) em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Spatial memory in sedentary and trained diabetic rats: Molecular mechanisms

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Neonatal anoxia in rats: hippocampal cellular and subcellular changes related to cell death and spatial memory

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Behavioural and neurochemical effects of phosphatidylserine in MPTP lesion of the substantia nigra of rats

The present study investigated the effects of intranigral MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) infusion on rats treated with phosphatidylserine and evaluated in two memory tasks and on striatal dopamine levels. The results indicated that MPTP produced a significant decrease in the avoidance number in comparison to sham-operated and non-operated rats submitted to a two-way avoidance task. MPTP-lesioned rats exhibited an increase in the latencies to find the platform in cued version of the water maze in comparison to sham-operated and non-operated animals. The tested toxin reduced striatal dopamine levels in comparison to sham-operated and non-operated groups. A final surprising result was that phosphatidylserine was unable to reverse the cognitive deficits produced by MPTP or the reduction of striatal dopamine levels. In conclusion, the data suggest that MPTP is a good model to study the early impairment associated with Parkinson's disease and phosphatidylserine did not improve the memory impairment induced by MPTP. (C) 2003 Elsevier B.V. All rights reserved.

Open elevated plus maze-induced antinociception in rats: A non-opioid type of pain inhibition?

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Water productivity assessment by using MODIS images and agrometeorological data in the Petrolina municipality, Brazil

The municipality of Petrolina, located in the semi-arid region of Brazil, is highlighted as an important agricultural growing region, however the irrigated areas have cleared natural vegetation inducing a loss of biodiversity. To analyze the contrast between these two ecosystems the large scale values of biomass production (BIO), evapotranspiration (ET) and water productivity (WP) were quantified. Monteithś equation was applied for estimating the absorbed photosynthetically active radiation (APAR), while the new SAFER (Simple Algorithm For Evapotranspiration Retrieving) algorithm was used to retrieve ET. The water productivity (WP) was analysed by the ratio of BIO by ET at monthly time scale with four bands of MODIS satellite images together with agrometeorological data for the year of 2011. The period with the highest water productivity values were from March to April in the rainy period for both irrigated and not irrigated conditions. However the largest ET rates were in November for irrigated crops and April for natural vegetation. More uniformity of the vegetation and water variables occurs in natural vegetation, evidenced by the lower values of standard deviation when comparing to irrigated crops, due to the different crop stages, cultural and irrigation managements. The models applied with MODIS satellite images on a large scale are considered to be suitable for water productivity assessments and for quantifying the effects of increasing irrigated areas over natural vegetation on regional water consumption in situations of quick changing land use pattern. © 2012 SPIE.

Large-Scale Water Productivity Assessments with MODIS Images in a Changing Semi-Arid Environment: A Brazilian Case Study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)