Polyamines play a critical role in the control of the innate immune response in the mouse central nervous system

The present work investigated whether polyamines play a role in the control of the innate immune response in the brain. The first evidence that these molecules may be involved in such a process was based on the robust increase in the expression of the first and rate-limiting enzyme of biosynthesis of polyamines during immune stimuli. Indeed, systemic lipopolysaccharide (LPS) administration increased ornithine decarboxylase (ODC) mRNA and protein within neurons and microglia across the mouse central nervous system (CNS). This treatment was also associated with a robust and transient transcriptional activation of genes encoding pro-inflammatory cytokines and toll-like receptor 2 (TLR2) in microglial cells. The endotoxin increased the cerebral activity of ODC, which was abolished by a suicide inhibitor of ODC. The decrease in putrescine levels largely prevented the ability of LPS to trigger tumor necrosis factor α and TLR2 gene transcription in the mouse brain. In contrast, expression of both transcripts was clearly exacerbated in response to intracerebral spermine infusion. Finally, inhibition of polyamine synthesis abolished neurodegeneration and increased the survival rate of mice exposed to a model of severe innate immune reaction in the CNS. Thus, polyamines have a major impact on the neuronal integrity and cerebral homeostasis during immune insults

Reconnaissance d'entités nommées : enrichissement d'un système à base de connaissances à partir de techniques de fouille de textes

International audienceIn this paper, we present and analyze the results obtained by our named entity recognition system, CasEN, during the Ester2 evaluation campaign. We identify on what difficulties our system was the most challenged, which mainly are: out-of-vocabulary words, metonymy and detection of the boundaries of named entities. Next, we propose a direction which may help us for improving performances of our system, by using exhaustive hierarchical and sequential data mining algorithms. This approach aims at extracting patterns corresponding to useful linguistic constructs for recognizing named entities. Finaly, we describe our experiments, give the results we currently obtain and analyze those results

Cell sizing of intact, flash-frozen adipose tissue

Histomorphometric analyses of adipose tissue usually require formalin fixation of fresh samples. Our objective was to determine if intact, flash-frozen whole adipose tissue samples stored at − 80 °C could be used for measurements developed for fresh-fixed adipose tissues. Portions of adipose tissue samples were either formalin-fixed immediately upon sampling or flash-frozen and stored at − 80 °C and then formalin-fixed during the thawing process. Mean adipocyte diameter was measured. Immunohistochemistry was performed on additional samples to identify macrophage subtypes (M1, CD14 + and M2, CD206 +) and total (CD68 +) number. All slides were counterstained using haematoxylin and eosin (H&E). Visual inspection of H&E-stained adipose tissue slides performed in a blinded fashion showed little or no sign of cell breakage in 74% of frozen-fixed samples and in 68% of fresh-fixed samples (p > 0.5). There was no difference in the distribution frequencies of adipocyte sizes in fresh-fixed vs. frozen-fixed tissues in both depots (p > 0.9). Mean adipocyte size from frozen-fixed samples correlated significantly and positively with adipocyte size from fresh-fixed samples (r = 0.74, p < 0.0001, for both depots). The quality of staining/immunostaining and appearance of tissue architecture were comparable in fresh-fixed vs. frozen-fixed samples. In conclusion, intact flash-frozen adipose tissue samples stored at − 80 °C can be used to perform techniques conventionally applied to fresh-fixed samples. This approach allows for retrospective studies with frozen human adipose tissue samples

Bone-marrow-derived microglia: myth or reality?

Microglia are the immune cells of the central nervous system (CNS). They patrol the brain environment with their ramifications and they respond quickly in the presence of pathogens and brain damages. Others and we have recently reported the existence of two different types of microglia, the resident and the newly differentiated microglia that are derived from the bone marrow stem cells. Of great interest is the fact that blood-derived microglial cells are associated with amyloid plaques and these cells are able to prevent the formation or eliminate the presence of amyloid deposits in mice that develop the major hallmark of Alzheimer's disease (AD). These cells are also recruited in the brain of other mouse models of brain diseases and acute injuries. They represent, therefore, a fantastic new vehicle for delivering key molecules to improve recovery, repair, and elimination of toxic proteins. However, recent studies have challenged this concept and raised concerns regarding the physiological relevance of bone-marrow-derived microglia. This review discusses both sides of the story and why the models used to follow the phenotypic fate of these cells are so crucial to reach the proper conclusion. Blood-derived progenitors have the ability to populate the CNS, especially during injuries and chronic diseases. However they do not do it in an efficient manner. Such a lack of proper recruitment may explain the delay in recovery and repair after acute damages and accumulation of toxic proteins in chronic brain diseases

Role of polyamines in the control of the immune response in the brain

Polyamines are essential polycations involved in a large variety of biological functions, including modulation of the nucleic acid conformation, RNA export and their degradation, protein synthesis, eIF-5A posttranslational modification, signal transduction, cell growth and differentiation, and tumor progression ( 1 –bi3. These various aspects in the biology of polyamines are addressed in other sections of this book

Emerging restorative treatments for Parkinson's disease.

Several exciting approaches for restorative therapy in Parkinson's disease have emerged over the past two decades. This review initially describes experimental and clinical data regarding growth factor administration. We focus on glial cell line-derived neurotrophic factor (GDNF), particularly its role in neuroprotection and in regeneration in Parkinson's disease. Thereafter, we discuss the challenges currently facing cell transplantation in Parkinson's disease and briefly consider the possibility to continue testing intrastriatal transplantation of fetal dopaminergic progenitors clinically. We also give a more detailed overview of the developmental biology of dopaminergic neurons and the potential of certain stem cells, i.e. neural and embryonic stem cells, to differentiate into dopaminergic neurons. Finally, we discuss adult neurogenesis as a potential tool for restoring lost dopamine neurons in patients suffering from Parkinson's disease