Age-Related Changes of Myelin Basic Protein in Mouse and Human Auditory Nerve

Age-related hearing loss (presbyacusis) is the most common type of hearing impairment. One of the most consistent pathological changes seen in presbyacusis is the loss of spiral ganglion neurons (SGNs). Defining the cellular and molecular basis of SGN degeneration in the human inner ear is critical to gaining a better understanding of the pathophysiology of presbyacusis. However, information on age-related cellular and molecular alterations in the human spiral ganglion remains scant, owing to the very limited availably of human specimens suitable for high resolution morphological and molecular analysis. This study aimed at defining age-related alterations in the auditory nerve in human temporal bones and determining if immunostaining for myelin basic protein (MBP) can be used as an alternative approach to electron microscopy for evaluating myelin degeneration. For comparative purposes, we evaluated ultrastructural alternations and changes in MBP immunostaining in aging CBA/CaJ mice. We then examined 13 temporal bones from 10 human donors, including 4 adults aged 38–46 years (middle-aged group) and 6 adults aged 63–91 years (older group). Similar to the mouse, intense immunostaining of MBP was present throughout the auditory nerve of the middle-aged human donors. Significant declines in MBP immunoreactivity and losses of MBP+ auditory nerve fibers were observed in the spiral ganglia of both the older human and aged mouse ears. This study demonstrates that immunostaining for MBP in combination with confocal microscopy provides a sensitive, reliable, and efficient method for assessing alterations of myelin sheaths in the auditory nerve. The results also suggest that myelin degeneration may play a critical role in the SGN loss and the subsequent decline of the auditory nerve function in presbyacusis

withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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Ultrastructural characterization of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid-induced cell death in embryonic dopaminergic neurons

Developing neuronal populations undergo significant attrition by natural cell death. Dopaminergic neurons in the substantia nigra pars compacta undergo apoptosis during synaptogenesis. Following this time window, destruction of the anatomic target of dopaminergic neurons results in dopaminergic cell death but the morphology is no longer apoptotic. We describe ultrastructural changes that appear unique to dying embryonic dopaminergic neurons. In primary cultures of mesencephalon, death of dopaminergic neurons is triggered by activation of glutamate receptors sensitive to alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA), and differs ultrastructurally from both neuronal apoptosis or typical excitotoxicity. AMPA causes morphological changes selectively in dopaminergic neurons, without affecting other neurons in the same culture dishes. Two hours after the onset of treatment swelling of Golgi complexes is apparent. At 3 h, dopaminergic neurons display loss of membrane asymmetry (coinciding with commitment to die), as well as nuclear membrane invagination, irregular aggregation of chromatin, and mitochondrial swelling. Nuclear changes continue to worsen until loss of cytoplasmic structures and cell death begins to occur after 12 h. These changes are different from those described in neurons undergoing either apoptosis or excitotoxic death, but are similar to ultrastructural changes observed in spontaneous death of dopaminergic neurons in the natural mutant weaver mouse.Fil: Dorsey, D. A.. Washington University in St. Louis; Estados UnidosFil: Masco, Daniel Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Washington University in St. Louis; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; ArgentinaFil: Dikranian, K.. Washington University in St. Louis; Estados UnidosFil: Hyrc, K.. Washington University in St. Louis; Estados UnidosFil: Masciotra, L.. Washington University in St. Louis; Estados UnidosFil: Faddis, B.. Washington University in St. Louis; Estados UnidosFil: Soriano, M.. Universidad de Valencia; EspañaFil: Gru, A. A.. Washington University in St. Louis; Estados UnidosFil: Goldberg, M. P.. Universidad de Valencia; España. Washington University in St. Louis; Estados UnidosFil: de Erausquin, Gabriel Alejandro. Washington University in St. Louis; Estados Unido

A simulation study of Top and Bottom Counting Detectors in ISS-CREAM experiment for cosmic ray electron physics

International audienceThe Cosmic Ray Energetics and Mass experiment at the International Space Station (ISS-CREAM) is developed for studying the origin, acceleration and propagation mechanism of high energy cosmic rays. The Top and Bottom Counting Detectors (TCD/BCD), sub-detectors of the ISS-CREAM instrument, are developed for electron/ γ -ray physics. The TCD/BCD help distinguish electrons from protons by comparing the hit and shower width distributions for electrons and protons. The e/p separation capability of the TCD/BCD is studied by using the GEANT3 simulation package, and optimal parameters for the e/p separation are obtained