1,721,003 research outputs found
Increased intracellular ionic content is correlated with a decreased perichromatin granule density in old neurones
No full textThe intracellular content of monovalent ions (Na+, Cl -, and K+) in brain cortical cells from young, adult, and old rats was measured by X-ray microanalysis. By referring the peak of each ion to the respective value of the dry mass, we obtained the intracellular content as a percentage of dry mass. A significant increase of the intracellular content of Na+, Cl-, and K+ was found in old animals. In the same type of cells from rats of different ages, we estimated the density of perichromatin granules (PGs), the RNA structural correlates containing ribonucleoproteins (RNPs). PGs were discovered by Bernhard's method, which allows the preferential staining of RNPs. The PG density (i.e., the number of PGs/μm2 of nuclear area) was significantly lower (-27.8%) in the neurons of old animals. Taken together, the present findings document that in the nuclei of brain cortical cells of old animals the ionic strength is markedly increased and that this alteration may affect chromatin functions (e.g., DNA template activity). The ionic content of the nucleoplasm is reported to modulate the structure of chromatin molecules and regulate gene expression; thus, the increased content of the three ions found by us in old animals, by increasing the viscosity of the nucleoplasm, may affect gene expression by disturbing the inhibition (negative regulation) or potentiation (positive regulation) of RNA polymerase binding. In physiological aging, increased ionic strength may lead to age-related DNA dysfunction as well as to alterations in the processing of RNA structural constituents, such as PGs. © 2004 New York Academy of Sciences
Involvement of the muscle–tendon junction in skeletal muscle atrophy: an ultrastructural study
No full textAging affects the distribution of the circadian CLOCK protein in rat hepatocytes.
No full textSeveral biochemical, physiological, and behavioral processes exhibit cyclic oscillations of about 24 h, which have been defined as circadian rhythms. In mammals, the primary circadian pacemaker resides in the suprachiasmatic nuclei; however, cell-autonomous circadian oscillators occur also in extraneural tissues, including the liver. CLOCK protein is a transcription factor essential for normal circadian rhythms and recent studies have demonstrated that it undergoes intranuclear redistribution in hepatocytes, along the daily cycle. It is known that aging leads to a progressive deterioration of the circadian rhythm at the behavioral, physiological, and cellular levels; in addition, aging affects the organization of nuclear structural components involved in transcription and splicing. In this view, we carried out ultrastructural immunocytochemical analyses on hepatocytes of adult and old rats, so as to investigate possible qualitative and quantitative modifications of CLOCK protein, in relation to the aging process. Our observations demonstrated that most CLOCK protein was always located in the cell nucleus, where it accumulated on perichromatin fibrils (the sites of premRNA transcription and early splicing); in addition, CLOCK showed daily oscillations in the different nuclear compartments, but these oscillations differed significantly between adult and old animals. This unusual distribution of CLOCK protein during aging could be related to the prolonged diurnal activity of old animals and/or to altered nuclear pathways. © 2005 Wiley-Liss, Inc
Brain, aging and neurodegeneration: Role of zinc ion availability
No full textActual fields of research in neurobiology are not only aimed at understanding the different aspects of brain aging but also at developing strategies useful to preserve brain compensatory capacity and to prevent the onset of neurodegenerative diseases. Consistent with this trend much attention has been addressed to zinc metabolism. In fact, zinc acts as a neuromodulator at excitatory synapses and has a considerable role in the stress response and in the functionality of zinc-dependent enzymes contributing to maintaining brain compensatory capacity. In particular, the mechanisms that modulate the free zinc pool are pivotal for safeguarding brain health and performance. Alterations in zinc homeostasis have been reported in Parkinson's and Alzheimer's disease as well as in transient forebrain ischemia, seizures and traumatic brain injury, but little is known regarding aged brain. There is much evidence that that age-related changes, frequently associated to a decline in brain functions and impaired cognitive performances, could be related to dysfunctions affecting the intracellular zinc ion availability. A general agreement emerges from studies of humans' and rodents' old brains about an increased expression of metallothionein (MT) isoforms I and II, but dyshomogenous results are reported for MT-III, and it is still uncertain whether these proteins maintain in aging the protective role, as it occurs in adult/young age. At the same time, there is considerable evidence that amyloid-β deposition in Alzheimer's disease is induced by zinc, but the pathological significance and the causes of this phenomenon are still an open question. The scientific debate on the role of zinc and of some zinc-binding proteins in aging and neurodegenerative disorders, as well as on the beneficial effect of zinc supplementation in aged brain and neurodegeneration, is extensively discussed in this review. © 2005 Elsevier Ltd. All rights reserved
Immunoproteasome in <i>Macaca fascicularis:</i> No Age-Dependent Modification of Abundance and Activity in the Brain and Insight into an <i>in silico</i> Structural Model
No full textIn this study, we investigated proteasome composition and activity in the brain of Macaca fascicularis, in order to test whether this nonhuman primate species might be a suitable animal model for anti-aging therapies in the central nervous system, addressed to the ubiquitin-proteasome system. We detected the catalytic β subunits of constitutive proteasome, as well as the PA28 regulator and a subunit of immunoproteasome (i.e., β1i [LMP2]), in seven adult, six old, and one young nonhuman primate brains. Subunit expression and proteasome activity were not influenced by the age of the animal in any of the brain regions (temporal and frontal cortex and cerebellum) we studied. However, an area-specific susceptibility to aged-related oxidative stress emerged. On the whole, the results suggest that, compared to humans, Macaca fascicularis primates may have a different age-dependent regulation of the ubiquitin-proteasome system and, possibly, of neuroinflammation in the brain. An in silico model of the 20S immunoproteasome containing the Macaca fascicularis α and β subunits, present in database or identified by our group (i.e., LMP2), has been developed. Additional information was obtained by de novo sequencing of the β1 (delta) subunit of Macaca fascicularis. A comparison with humans suggests that in multiprotein complexes some functional subunits, such as α subunits, appear to be preferentially conserved during evolution.In this study, we investigated proteasome composition and activity in the brain of Macaca fascicularis, in order to test whether this nonhuman primate species might be a suitable animal model for anti-aging therapies in the central nervous system, addressed to the ubiquitin-proteasome system. We detected the catalytic β subunits of constitutive proteasome, as well as the PA28 regulator and a subunit of immunoproteasome (i.e., β1i [LMP2]), in seven adult, six old, and one young nonhuman primate brains. Subunit expression and proteasome activity were not influenced by the age of the animal in any of the brain regions (temporal and frontal cortex and cerebellum) we studied. However, an area-specific susceptibility to aged-related oxidative stress emerged. On the whole, the results suggest that, compared to humans, Macaca fascicularis primates may have a different age-dependent regulation of the ubiquitin-proteasome system and, possibly, of neuroinflammation in the brain. An in silico model of the 20S immunoproteasome containing the Macaca fascicularis α and β subunits, present in database or identified by our group (i.e., LMP2), has been developed. Additional information was obtained by de novo sequencing of the β1 (delta) subunit of Macaca fascicularis. A comparison with humans suggests that in multiprotein complexes some functional subunits, such as α subunits, appear to be preferentially conserved during evolution
Synaptic remodelling in hippocampal CA1 area of aged rats following passive avoidance task correlates with good memory performance
No full textNeuronal plasticity in aging: a quantitative immunohistochemical study of GAP-43 distribution in discrete regions of the rat brain.
No full textAge-related changes in neuroplasticity have been investigated considering the neuronal growth-associated protein GAP-43 as a marker of nerve cell structural adaptive capabilities. We carried out a quantitative immunohistochemical study on the distribution of GAP-43 in the molecular layer of the cerebellar cortex, in the inner molecular layer of the hippocampal dentate gyrus, in the stratum radiatum of the CA1 region, in layer 1 of the cingulate cortex and in the nerve fiber layer of the main olfactory bulb of 3-, 18- and 31-month-old Wistar rats. A decrease of GAP-43 immunoreactivity was observed in the old rats in comparison with the adult animals in all the 5 areas analyzed, although these variations were only statistically significant in the dentate gyrus, cingulate cortex and olfactory bulb. In these latter zones, GAP-43 immunolabeling is reduced by 54, 42 and 38%, respectively, in the old versus the adult group. Comparing these data with the age-dependent decrease of neuron density innervating the areas investigated, we support the hypothesis that the decline of GAP-43 observed in old animals documents a consistent reduction of axon plasticity in the inner molecular layer of the dentate gyrus and in layer 1 of the cingulate cortex. These results suggest an important role of GAP-43 as a marker of age-dependent deterioration of synaptic plasticity, especially in those areas of the brain involved in memory and emotional behavior
Perichromatin fibrils accumulation in hepatocyte nuclei reveals alterations of pre-mRNA processing during ageing.
No full textAgeing affects transcription and splicing in rat hepatocytes
No full textThe work describes the effects of ageing on transcription and splicing in rat hepatocyte
Immunolocalization of the circadian Clock protein in hepatocytes of adult and old rats
No full textThe work reports the immunolocalization of the circadian Clock protein in hepatocytes of adult and old rat
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