Apolipoprotein E-Mimetics Inhibit Neurodegeneration and Restore Cognitive Functions in a Transgenic Drosophila Model of Alzheimer's Disease

Background

Mutations of the amyloid precursor protein gene (APP) are found in familial forms of Alzheimer''s disease (AD) and some lead to the elevated production of amyloid-β-protein (Aβ). While Aβ has been implicated in the causation of AD, the exact role played by Aβ and its APP precursor are still unclear.

Principal Findings

In our study, Drosophila melanogaster transgenics were established as a model to analyze AD-like pathology caused by APP overexpression. We demonstrated that age related changes in the levels and pattern of synaptic proteins accompanied progressive neurodegeneration and impairment of cognitive functions in APP transgenic flies, but that these changes may be independent from the generation of Aβ. Using novel peptide mimetics of Apolipoprotein-E, COG112 or COG133 proved to be neuroprotective and significantly improved the learning and memory of APP transgenic flies.

Conclusions

The development of neurodegeneration and cognitive deficits was corrected by injections of COG112 or COG133, novel mimetics of apolipoprotein-E (apoE) with neuroprotective activities.     

The influence of nitric oxide inductor (NaNO2) on the sensitivity of Chinese hamster cells to hyperthermia

Formerly we reported the reduction of sensitivity to gamma- and UV-radiation in Chinese hamster cells of line 90 under the influence of nitric oxide inductor (NaNO2). Of interest was to learn if it possible to reduce the influence of hyperthermia on cells by means of NO inductor. A 1 h long incubation with this NO donor demonstrated an increased survival of cells heated up to 45 degrees C, and a decreased frequency of chromosomal aberrations in these. Employment of cycloheximide (CHE), an inhibitor of protein synthesis, and administration of CHE together with nitric oxide donor (NaNO2), equally increased the cell survival at hyperthermia. These and relevant literature data suggest that the demonstrated effect of exogenous NO may be associated with HSP70 protein. The noticed decrease in the number of chromosomal aberrations in heated cells under the influence of NO donor may play an important role in its modifying effect on cells at hyperthermia.     

Inhibitory effect of active oxygen scavengers on the endocytosis of concanavalin A by lymphocytes

It has been shown that of active oxygen species regulate the activity of the processes of Con A endocytosis in rat thymus cells.     

Presynaptic and Postsynaptic Effects of Neuropeptide Y in the Rat Pineal Gland

Abstract: Neuropeptide Y is colocalized with noradrena-line in sympathetic fibers innervating the rat pineal gland. In this article we present a study of the effects and mechanisms of action of neuropeptide Y on the pineal noradrenergic transmission, the main input leading to the rhythmic secretion of melatonin. At the presynaptic level, neuropeptide Y inhibits by 45%, with an EC₅₀ of 50 n M , the potassium-evoked noradrenaline release from pineal nerve endings. This neuropeptide Y inhibition occurs via the activation of pertussis toxin-sensitive G protein-coupled neuropeptide Y-Y2 receptors and is independent from, but additive to, the α₂-adrenergic inhibition of noradrenaline release. At the postsynaptic level, neuropeptide Y decreases by a maximum of 35%, with an EC₅₀ of 5 n M , the β-adrenergic induction of cyclic AMP elevation via the activation of neuropeptide Y-Y1 receptors. This moderate neuropeptide Y-induced inhibition of cyclic AMP accumulation, however, has no effect on the melatonin secretion induced by a β-adrenergic stimulation. On the contrary, in the presence of 1 m M ascorbic acid, neuropeptide Y potentiates (up to threefold) the melatonin secretion. In conclusion, this study has demonstrated that neuropeptide Y modulates the noradrenergic transmission in the rat pineal gland at both presynaptic and postsynaptic levels, using different receptor subtypes and transduction pathways.     

The core domain of retrotransposon integrase in Hordeum: predicted structure and evolution

Propagation of long terminal repeat (LTR)-bearing retrotransposons and retroviruses requires integrase (IN, EC 2.7.7.-), encoded by the retroelements themselves, which mediates the insertion of cDNA copies back into the genome. An active retrotransposon family, BARE-1, comprises approximately 7% of the barley (Hordeum vulgare subsp. vulgare) genome. We have generated models for the secondary and tertiary structure of BARE-1 IN and demonstrate their similarity to structures for human immunodeficiency virus 1 and avian sarcoma virus INs. The IN core domains were compared for 80 clones from 28 Hordeum accessions representative of the diversity of the genus. Based on the structural model, variations in the predicted, aligned translations from these clones would have minimal structural and functional effects on the encoded enzymes. This indicates that Hordeum retrotransposon IN has been under purifying selection to maintain a structure typical of retroviral INs. These represent the first such analyses for plant INs.      

Evolution of anaerobic ciliates from the gastrointestinal tract: phylogenetic analysis of the ribosomal repeat from Nyctotherus ovalis and its relatives

The 18S and 5.8S rDNA genes and the internal transcribed spacers ITS-1 and ITS-2 of ciliates living in the hindgut of frogs, millipedes, and cockroaches were analyzed in order to study the evolution of intestinal protists. All ciliates studied here belong to the genus Nycrotherus. Phylogenetic analysis revealed that these ciliates from a monophyletic group that includes the distantly related anaerobic free-living heterotrichous ciliates Metopus palaeformis and Metopus contortus. The intestinal ciliates from the different vertebrate and invertebrate hosts are clearly divergent at the level of their rDNA repeats. This argues for the antiquity of the associations and a predominantly vertical transmission. This mode of transmission seems to be controlled primarily by the behavior of the host. The different degrees of divergence between ciliates living in different strains of one and the same cockroach species most likely reflect the different geographical origins of the hosts. In addition, host switches must have occurred during the evolution of cockroaches, since identical ciliates were found only in distantly related hosts. These phenomena prevent the reconstruction of potential cospeciation events.      

Genetic Transformation of Wheat: State of the Art

The review provides the latest achievements in the field of wheat transformation and analysis of the factors affecting transformation efficiency. A comparative analysis of the most commonly used methods of wheat transformation, i.e., direct gene transfer by biolistic transformation and by Agrobacterium tumefaciens in vitro and in planta, is carried out. The stages and components of methods that affect transformation efficiency are examined in detail. Since the first successful biolistic transformation of wheat in 1992 and Agrobacterium- mediated transformation in 1997, 25 to 20 years have passed. Since then, all physical and biological parameters for the heterologous DNA delivery to the wheat genome and regeneration of plant transformants in vitro have been investigated and described in detail. Information on the influence of key parameters and factors on increasing transformation efficiency of highly productive wheat varieties is presented.     

Feeding habits of harp seals (Phoca groenlandica) during early summer and autumn in the northern Barents Sea

The feeding habits of harp seals (Phoca groenlandica) in the Barents Sea were examined in studies conducted during June 1991, September 1990 and 1991, and October 1992. Analyses of stomach and intestinal contents were carried out and concurrent estimates of prey abundance were made using trawl gear. Harp seals appeared to feed at low intensity in the pack ice belt during the first half of June. There was little potential prey in the water column, but prawns (Pandalus borealis), capelin (Mallotus villosus) and polar cod (Boreogadus saida) were abundant close to the bottom. In September, the seals sampled in the northern pack ice areas of the Barents Sea fed on the pelagic amphipod Parathemisto libellula, krill (Thysanoessa spp.), prawns and, to a lesser extent, on fish species such as polar cod, sculpins (Cottidae) and snailfish (Liparidae). Trawling revealed that large quantities of Parathemisto libellala were present in the upper layers of the water column. Fish, mainly capelin and polar cod, were less abundant and occurred in deeper waters. In mid-October, the diet of seals in the northern Barents Sea consisted mainly of amphipods (Parathemisto sp.). Later in October, when increasing pack ice cover forced the harp seals to move south, the diet seemed to change from amphipods to fish prey, predominantly capelin and polar cod.