Distinct Transcriptome Expression of the Temporal Cortex of the Primate Microcebus murinus during Brain Aging versus Alzheimer's Disease-Like Pathology

Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD). However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix). Gene expression profiles were assessed in the temporal cortex of 6 young adults, 10 healthy old animals and 2 old, “AD-like” animals that presented ß-amyloid plaques and cortical atrophy, which are pathognomonic signs of AD in humans. Gene expression data of the 14,911 genes that were detected in at least 3 samples were analyzed. By SAM (significance analysis of microarrays), we identified 47 genes that discriminated young from healthy old and “AD-like” animals. These findings were confirmed by principal component analysis (PCA). ANOVA of the expression data from the three groups identified 695 genes (including the 47 genes previously identified by SAM and PCA) with significant changes of expression in old and “AD-like” in comparison to young animals. About one third of these genes showed similar changes of expression in healthy aging and in “AD-like” animals, whereas more than two thirds showed opposite changes in these two groups in comparison to young animals. Hierarchical clustering analysis of the 695 markers indicated that each group had distinct expression profiles which characterized each group, especially the “AD-like” group. Functional categorization showed that most of the genes that were up-regulated in healthy old animals and down-regulated in “AD-like” animals belonged to metabolic pathways, particularly protein synthesis. These data suggest the existence of compensatory mechanisms during physiological brain aging that disappear in “AD-like” animals. These results open the way to new exploration of physiological and “AD-like” aging in primates

Multiple Changes in Peptide and Lipid Expression Associated with Regeneration in the Nervous System of the Medicinal Leech

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Effect of cattle slurry pre-treatment by separation and addition of nitrification inhibitors on gaseous emissions and N dynamics: A laboratory study

The application of untreated or treated animal manure to soils can result in increased N and C gaseous emissions contributing to ecosystem change and global warming. In the present study, dairy cattle slurry (liquid manure) was subjected first to pre-treatment by separation using a screw press to obtain a liquid (LF) and a solid fraction (SF). Then, the different fractions and the whole slurry (WS) were combined with two nitrification inhibitors (NI), dicyandiamide (DCD) or 3,4-dimethylpyrazole phosphate (DMPP), were applied to soil to assess the effect of slurry treatment by separation and NI addition on soil N dynamics and CH4, CO2, NH3, NO and N2O emissions. The WS and the two slurry fractions, combined or not with DCD or DMPP, were applied to soil at an equivalent field dosage of 120 kg total N haÿ1 . Controls including a soil only, soil–DCD and soil–DMPP treatments were also included. The mixtures were incubated for 93-d at 20 °C. Results obtained show that NI inhibited nitrification between 16 and 30-d in WS and LF, with DMPP having a longer effect over time compared to DCD. There was no significant effect of NI on nitrification for the SF treatment. Nitrification inhibitors did not significantly affect (P > 0.05) the CH4, CO2 and N2O emissions, but significantly decreased (P < 0.05) NO emissions. Furthermore, the two NIs had a similar effect on gaseous emissions. Throughout the entire experiment, the greatest amount of NO was released from the LF treatment (without NI), while the greatest amount of N2O was released from the SF treatment. Slurry separation had no impact on N emissions, while the combination of this process with one of the two NI led to a small reduction in total N emissions

Rapid regulation of endoplasmic reticulum dynamics in dendritic spines by NMDA receptor activation

Endoplasmic reticulum (ER) is motile within dendritic spines, but the mechanisms underlying its regulation are poorly understood. To address this issue, we have simultaneously imaged morphology and ER content of dendritic spines in cultured dissociated mouse hippocampal neurons. Over a 10 min period, spines were highly dynamic, with spines both increasing and decreasing in volume. ER was present in approximately 50% of spines and was also highly dynamic, with a net increase over this period of time. Inhibition of the endogenous activation of NMDA receptors resulted in a reduction in ER growth. Conversely, augmentation of the synaptic activation of NMDA receptors, by elimination of striatal-enriched protein tyrosine phosphatase (STEP), resulted in enhanced ER growth. Therefore, NMDA receptors rapidly regulate spine ER dynamics.</p

A STEP forward in neural function and degeneration

STriatal-Enriched Phosphatase (STEP) is a brain-specific protein tyrosine phosphatase that plays a role in synaptic plasticity and has recently been implicated in neurodegenerative disease. STEP opposes the development of synaptic strengthening by dephosphorylating and inactivating key signaling proteins that include the MAP kinases ERK1/2 and p38, as well as the tyrosine kinase Fyn. STEP also dephosphorylates the GluR2 subunit of the AMPAR and the NR2B subunit of the NMDAR, which leads to internalization of the NR1/NR2B and GluR1/GluR2 receptors. STEP levels and activity are regulated through phosphorylation, local translation, ubiquitination and degradation and proteolytic cleavage. Here we review recent progress in understanding the normal regulation of STEP and how this regulation is disrupted in Alzheimer's disease, in which abnormally increased STEP levels and activity contribute to the cognitive deficits