Evolution of the Aging Brain Transcriptome and Synaptic Regulation

Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD) and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4). However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes

Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention

Analyse génétique et métabolique de la lipogénèse aviaire dans des cellules d'origine hépatique en culture

*INRA, Centre de Rennes Diffusion du document : INRA, Centre de Rennes Diplôme : Dr. d'Universit

Analyse génétique et métabolique de la lipogénèse aviaire dans des cellules d'origine hépatique en culture

*INRA, Centre de Rennes Diffusion du document : INRA, Centre de Rennes Diplôme : Dr. d'Universit

Lipogenesis in cultured chicken hepatocytes and chicken hepatocellular carcinoma cell line LMH

*INRA, Laboratoire Associe INRA-ENSAR de Genetique Animale, 35042 Rennes Diffusion du document : INRA, Laboratoire Associe INRA-ENSAR de Genetique Animale, 35042 RennesNational audienc

Lipogenesis in cultured chicken hepatocytes and chicken hepatocellular carcinoma cell line LMH

*INRA, Laboratoire Associe INRA-ENSAR de Genetique Animale, 35042 Rennes Diffusion du document : INRA, Laboratoire Associe INRA-ENSAR de Genetique Animale, 35042 RennesNational audienc

Adult chicken hepatocytes in primary cultures for the study of lipogenesis

* INRA, centre de Rennes Diffusion du document : INRA, centre de RennesInternational audienc

Adult chicken hepatocytes in primary cultures for the study of lipogenesis

* INRA, centre de Rennes Diffusion du document : INRA, centre de RennesInternational audienc

Gene transfer into chicken hepatocytes in primary culture and HepG2 hepatoma cells: ex vivo models to study lipid metabolism regulations

International audienc