Peripapillary intrachoroidal cavitation at the crossroads of peripapillary myopic changes

AIM: To analyze the prevalence of peripapillary intra-choroidal cavitation (PICC) in eyes with gamma peripapillary atrophy (γPPA), in eyes with peripapillary staphyloma (PPS) and in those combining γPPA and PPS and to analyze border tissue discontinuity in PICC. METHODS: This prospective cross-sectional non interventional study included highly myopic eyes. Non-highly myopic eyes were used as control. Radial and linear scans centered on the optic nerve head were performed using spectral-domain optical coherence tomography. Variables were analyzed along the twelve hourly optical coherence tomography sections in both eyes of each subject. RESULTS: A total of 667 eyes of 334 subjects were included: 229 (34.3%) highly myopic eyes and 438 (65.7%) non highly myopic eyes. The mean age of the highly myopic group was 48.99±17.81y. PICC was found in a total of 40 eyes and in 13.2% (29/220) of highly myopic eyes. PICC was found in 10.4% (40/386) of eyes with γPPA, in 20.5% (40/195) of eyes with PPS and in 22.7% (40/176) of those combining γPPA and PPS. All the eyes with PICC showed the co-existence of γPPA and PPS whereas none of the eyes presenting only one of these entities exhibited PICC. A border tissue discontinuity in the γPPA area was found in all eyes with PICC. CONCLUSION: We confirm the presence of a border tissue discontinuity in the γPPA area of all eyes with PICC. These findings suggest the involvement of mechanical factors in the pathogenesis of PICC which may contribute to PICC-related visual field defects

Deletion of Irs2 reduces amyloid deposition and rescues behavioural deficits in APP transgenic mice

As impaired insulin signalling (IIS) is a risk factor for Alzheimer's disease we crossed mice (Tg2576) over-expressing human amyloid precursor protein (APP), with insulin receptor substrate 2 null (Irs2(-/-)) mice which develop insulin resistance. The resulting Tg2576/Irs2(-/-) animals had increased tau phosphorylation but a paradoxical amelioration of Abeta pathology. An increase of the Abeta binding protein transthyretin suggests that increased clearance of Abeta underlies the reduction in plaques. Increased tau phosphorylation correlated with reduced tau-phosphatase PP2A, despite an inhibition of the tau-kinase glycogen synthase kinase-3. Our findings demonstrate that disruption of IIS in Tg2576 mice has divergent effects on pathological processes-a reduction in aggregated Abeta but an increase in tau phosphorylation. However, as these effects are accompanied by improvement in behavioural deficits, our findings suggest a novel protective effect of disrupting IRS2 signalling in AD which may be a useful therapeutic strategy for this condition

La glycogène synthase kinase-3B: rôle dans l'étiopathogénie et dans la régulation fonctionnelle du cytosquelette microtubulaire

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Guide des travaux pratiques d'histologie

MED2 - MEDC117info:eu-repo/semantics/published

Developmental expression and localization of glycogen synthase kinase-3beta in rat brain.

Glycogen synthase kinase (GSK)-3beta is a protein kinase in the wingless/wnt pathway and as such is involved in the regulation of growth and development of the neural tissue in Drosophila and in vertebrates. This enzyme is also abundantly expressed in the mammal adult brain, where it might play a role in the regulation of several substrates. The expression and the neuroanatomical distribution of GSK-3beta immunoreactivity in the rat brain from embryonic up to adult stages has been studied. GSK-3beta was expressed in the developing brain with the highest expression observed from 18 days of embryonic life up to 10 days of postnatal life. Its expression decreased thereafter and was lowest in the adult. GSK-3beta was strongly expressed in developing neurons but only weakly expressed in layers containing neuroblasts. In the adult and during development, GSK-3beta was detected in the pericarya and proximal part of dendrites. In the embryo, an intense GSK-3beta immunoreactivity was also observed in axonal tracts. This axonal immunoreactivity had markedly decreased by 10 days of postnatal life and was absent at 20 days of postnatal life and in the adult. No GSK-3beta immunoreactivity was detected in astrocytes. The GSK-3beta immunoreactivity was found in most brain regions, although significant local variations of GSK-3beta expression were observed. The developmental evolution of GSK-3beta compartmentalization in neurons parallels that of phosphorylated tau, a protein considered to be a physiological substrate for the kinase.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Increased level of active GSK-3β in Alzheimer's disease and accumulation in argyrophilic grains and in neurones at different stages of neurofibrillary degeneration

SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Guide des travaux pratiques d'histologie

MED2, MEDC117info:eu-repo/semantics/published

Guide des travaux pratiques d'histologie

MED2, MEDC117info:eu-repo/semantics/published

Plaques amyloïdes et pathologie tau : modélisation de leur interaction dans des modèles murins développant les lésions de la maladie d’Alzheimer

info:eu-repo/semantics/publishe

Motor Deficit in a Tauopathy Model Is Induced by Disturbances of Axonal Transport Leading to Dying-Back Degeneration and Denervation of Neuromuscular Junctions

Several neurodegenerative diseases are characterized by both cognitive and motor deficits associated with accumulation of tau aggregates in brain, brainstem, and spinal cord. The Tg30 murine tauopathy model expresses a human tau protein bearing two frontotemporal dementia with Parkinsonism linked to chromosome 17 pathogenic mutations and develops a severe motor deficit and tau aggregates in brain and spinal cord. To investigate the origin of this motor deficit, we analyzed the age-dependent innervation status of the neuromuscular junctions and mutant tau expression in Tg30 mice. The human transgenic tau was detected from postnatal day 7 onward in motoneurons, axons in the sciatic nerve, and axon terminals of the neuromuscular junctions. The development and maturation of neuromuscular junctions were not disrupted in Tg30 mice, but their maintenance was disturbed in adult Tg30 mice, resulting in a progressive and severe muscle denervation. This muscle denervation was associated with early electrophysiological signs of muscle spontaneous activities and histological signs of muscle degeneration. Early loss of synaptic vesicles in axon terminals preceding motor deficits, accumulation of Gallyas-positive aggregates, and cathepsin-positive vesicular clusters in axons in the sciatic nerve suggest that this denervation results from disturbances of axonal transport. This physiopathological mechanism might be responsible for motor signs observed in some human tauopathies, and for synaptic dysfunction resulting from alterations at the presynaptic level in these diseases.SCOPUS: ar.jinfo:eu-repo/semantics/publishe