Role de l'astroglie et interactions avec la microglie dans le developpement du systeme nerveux central de souris: approches cellulaire et moleculaire

Available from INIST (FR), Document Supply Service, under shelf-number : T 84775 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Steroidogenic Enzyme Expression in the Rat Cochlea

Objective-Steroid hormones, and particularly mineralocorticoids, are candidates for controlling the homeostasis of endolymph as steroid receptors are widely expressed in the cochlea. In contrast, experiments on adrenalectomized animals have shown that an absence of steroids had little effect on the ionic composition of endolymph and hearing ability. We thus hypothesized that local production of steroids in the inner ear may regulate cochlear fluid exchanges. Results-Using reverse transcription -polymerase chain reaction techniques, we showed that transcripts encoding the P450 side-chain cleavage, the 3beta hydroxysteroid dehydrogenase (3 beta HSD) and the 17alpha hydroxylase (P450 C17) were expressed in the lateral wall, organ of Corti and modiolus. The mRNA encoding aldosterone synthase was expressed in the modiolus and lateral wall while the P450 11 beta1 hydroxylase was not detected at all in any of these tissues. In situ hybridization experiments on cochlear sections confirmed that the 3beta HSD transcripts were expressed in the spiral ligament and modiolus and possibly in the hair cells of the organ of Corti. However, it was not possible to detect P450 C17 transcripts. Immunohistochemistry performed with an antibody raised against the various 3beta HSD isoforms confirmed the localization found using in situ hybridization . Conclusions-These results suggest that enzymes of the steroid pathway leading to mineralocorticoids and sex steroid hormones, but not glucocorticoids, may be expressed in the rat cochlea. This work is in line with the recent description of local production of steroid hormones in the brain ( neurosteroids), heart and skin. In the cochlea, the local production of mineralo and sex steroids could account for a paracrine role and could induce specific gene expression through steroid receptors or act via a non - genomic mechanism on membrane receptors or ionic exchangers. Experiments aimed at demonstrating enzymatic activities within cochlea tissues are in progress

Apoptosis in the Retina

Retinal degenerations are a common cause of blindness in Western countries. Despite various origins of retinal degeneration it is well recognised that. Apoptosis is the final pathway of photoreceptor neuron cell death in these diseases. So that Ivana Scovassi presents the historical development of our knowledge in: apoptosis, its difference with other forms of cell death as necrosis and analyses when and how apoptosis arises, discussing also the molecular markers in this form of cell death. This introductory chapter is followed by a paper of Rafael Linden analysing apoptosis in retinal development. He reviews evidence that tissue specific components controls cell death. In this context the roles of gap junctions, of the extra cellular matrix, and of neurotransmitters and neuropeptides are discussed. The data support the view that histotypical networks impinge upon cell-autonomous mechanisms. Neural cells are very difficult to replace so that they are highly protected from apoptosis and mostly from the action of caspases, the more efficient effectors in this type of cell death. So that caspase independent pathways are extensively discussed in the chapter written by E. Martin and A. Torriglia. In the following chapters discuss the activation of apoptosis in different retinal pathologies. Dr. Barber analyses apoptosis in diabetic retinopathy, which may seem paradoxical since the disease culminates in the proliferation of vascular endothelial cells. However experimental data suggest that apoptosis occurs in the neural cells of the retina soon after the onset of diabetes. Apoptosis in retinal degeneration, is analysed by Dejneka and Rex that provide examples of inherited, induced and acquired retinal degenerations, including retinitis pigmentosa, cancer-associated retinopathy, retinal detachment and lead toxicity. A very frequent retinal pathology is glaucoma, disease affecting mostly ganglion cells. Recent advances in this topic are discussed in the chapter written by P. Lassiaz and B. Omri. Finally two chapters deal with the relevance of RPE cells in retinal physiology by underling the effects of apoptosis in this non neural cells in development (Marc Abitbol) and pathology Frederic Mascarelli). This book is far for been exhaustive and covers a limited part of the knowledge in the subject. We hope to provide readers with a series of basical research in the field helping to understand cellular basis of retinal pathology

The role of PKCzeta in NMDA-induced retinal ganglion cell death: prevention by aspirin.

Intravitreal NMDA injection has been shown to induce the excitotoxic loss of retinal cells. The retinal ganglion cell apoptosis induced by NMDA is thought to play an important role in retinal ischemia injury and NMDA-injected rat has been used as a model of neuronal loss in diseases such as glaucoma. In this experimental model, we studied the early effects of NMDA leading to the degeneration of retinal ganglion cells. PKCzeta regulates the NF-kappaB pathway in cellular responses to various stresses and we have shown that aspirin inhibits purified human PKCzeta. We therefore investigated the molecular mechanism by which retinal cells limit ocular injury following NMDA treatment. We found that the NMDA-induced apoptosis of ganglion cells was mediated, at least partly, by PKCzeta. This enzyme was activated early in the cellular response to NMDA. Prolonged activation was followed by PKCzeta cleavage, and nuclear translocation of the C-terminal region of this protein-a critical event for the survival of retinal cells. We also found that pretreatment with aspirin or the coinjection of NMDA with a specific PKCzeta inhibitor counteracted the effects of NMDA. These findings provide new insight into the role played by PKCzeta in neuronal loss in glaucoma

Outcome of permanent vascular access for haemodialysis in patients with end-stage renal disease in Cameroon: Results from the pilot experience of the Douala general hospital

Background: Chronic Kidney disease is a major health problem in the world. Native arteriovenous Fistula (AVF) is well established as the best vascular access for haemodialysis. Little is known about the outcome of AVF in sub-Saharan Africa. We aim to analyze the outcome of patients undergoing AVF creation during the pilot program established at the Douala general hospital (DGH). Method: This was hospital-based, longitudinal study with a retrospective phase (April 2010-January 2014) and a prospective phase (January 2014-April 2014). All consecutive patients operated for AVF creation were included in this study. Socio-demographics data, functionality, and complications were analyzed. Results: Eighty-one patients including 52 men were enrolled in this study (49 prospectively and 32 retrospectively). The mean age was 52, 3 years (range 18-81 years). Hypertension (66, 7%), diabetes (17, 3%), and HIV (8, 6%) were the most observed co-morbidities. About 96.3% of AVF were native and 3.7% were prosthetic graft. Radiocephalic AVF was performed at a rate of 77.8%. The primary function rate was 97.7% and the mean follow-up period 43.4 weeks. The overall rate of complications was 44.4% of whom 30.5% were early, 30.5% secondary, and 39% lasted. The treatment of these complications was conservative in 48.7% of cases. Conclusions: The results of the pilot program of AVF creation at the DGH are encouraging. However, the sustainability of this project requires human capacity building.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The role of PKCzeta in amikacin-induced apoptosis in the cochlea: prevention by aspirin.

Aminoglycoside antibiotics are ototoxic, inducing irreversible sensorineural hearing loss mediated by oxidative and excitotoxic stresses. The NF-kappaB pathway is involved in the response to aminoglycoside damage in the cochlea. However, the molecular mechanisms of this ototoxicity remain unclear. We investigated the expression of PKCzeta, a key regulator of NF-kappaB activation, in response to aminoglycoside treatment. Amikacin induced PKCzeta cleavage and nuclear translocation. These events were concomitant with chromatin condensation and paralleled the decrease in NF-kappaB (p65) levels in the nucleus. Amikacin also induced the nuclear translocation of apoptotic inducing factor (AIF). Prior treatment with aspirin prevented PKCzeta cleavage and nuclear translocation. Thus, aspirin counteracts the early effects of amikacin, thereby protecting hair cells and spiral ganglion neurons. These results demonstrate that PKCzeta acts as sentinel connecting specific survival pathways to mediate cellular responses to amikacin ototoxicity