Age-Related Mitochondrial Alterations without Neuronal Loss in the Hippocampus of a Transgenic Model of Alzheimer's Disease

2013 ◽  
Vol 10 (4) ◽  
pp. 390-405 ◽  
Author(s):  
Mar Cuadrado-Tejedor ◽  
Jesus Felipe Cabodevilla ◽  
Marta Zamarbide ◽  
Teresa Gomez-Isla ◽  
Rafael Franco ◽  
...  
Keyword(s):  
Neuronal Loss ◽  
Transgenic Model ◽  
Mitochondrial Alterations ◽  
Age Related

scholarly journals Apoptosis in the Extraosseous Calcification Process

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 131
Author(s):  
Federica Boraldi ◽  
Francesco Demetrio Lofaro ◽  
Daniela Quaglino
Keyword(s):  
Genetic Basis ◽  
Membrane Vesicles ◽  
Matrix Vesicles ◽  
Apoptotic Bodies ◽  
Connective Tissues ◽  
Mineralization Process ◽  
Mitochondrial Alterations ◽  
Age Related ◽  
And Oxidative Stress ◽  
And Cartilage

Extraosseous calcification is a pathologic mineralization process occurring in soft connective tissues (e.g., skin, vessels, tendons, and cartilage). It can take place on a genetic basis or as a consequence of acquired chronic diseases. In this last case, the etiology is multifactorial, including both extra- and intracellular mechanisms, such as the formation of membrane vesicles (e.g., matrix vesicles and apoptotic bodies), mitochondrial alterations, and oxidative stress. This review is an overview of extraosseous calcification mechanisms focusing on the relationships between apoptosis and mineralization in cartilage and vascular tissues, as these are the two tissues mostly affected by a number of age-related diseases having a progressively increased impact in Western Countries.

scholarly journals Age-related neuronal loss in the rat brain starts at the end of adolescence

2012 ◽  
Vol 6 ◽  
Author(s):  
Priscilla Morterá ◽  
Suzana Herculano-Houzel
Keyword(s):  
Rat Brain ◽  
Neuronal Loss ◽  
Age Related

Postreceptor Neuronal Loss in Intermediate Age-related Macular Degeneration

2017 ◽  
Vol 181 ◽  
pp. 1-11 ◽  
Author(s):  
Enrico Borrelli ◽  
Nizar Saleh Abdelfattah ◽  
Akihito Uji ◽  
Muneeswar Gupta Nittala ◽  
David S. Boyer ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Neuronal Loss ◽  
Age Related Macular Degeneration ◽  
Age Related

scholarly journals Severe and regionally-widespread increases in tissue urea in the human brain represent a novel finding of pathogenic potential in Parkinson’s disease dementia

2021 ◽  
Author(s):  
Melissa Scholefield ◽  
Stephanie J. Church ◽  
Jingshu Xu ◽  
Stefano Patassini ◽  
Federico Roncaroli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Performance ◽  
Current Knowledge ◽  
Neuronal Loss ◽  
Middle Temporal Gyrus ◽  
Parkinson’S Disease Dementia ◽  
Pathogenic Potential ◽  
Age Related ◽  
Liquid Chromatography Tandem Mass

Abstract Background: Widespread elevations in brain urea have, in recent years, been reported in certain types of age-related dementia, notably Alzheimer’s disease (AD) and Huntington’s disease (HD). Urea increases in these diseases are substantive, and approximate in magnitude to levels present in uraemic encephalopathy. In AD and HD, elevated urea levels occur across the entire brain, and not only in regions heavily affected by neurodegeneration. However, measurements of brain urea have not hitherto been reported in Parkinson’s disease dementia (PDD), a condition defined by changes in thinking and behaviour in someone with a diagnosis of Parkinson's disease, which shares neuropathological and symptomatic overlap with both AD and HD. This study aims to address this gap in the current knowledge of PDD.Methods: Here we report measurements of tissue urea from nine neuropathologically-confirmed regions of the brain in PDD and post-mortem-delay-matched controls, in regions that included the cerebellum, motor cortex, sensory cortex, hippocampus, substantia nigra, middle temporal gyrus, medulla oblongata, cingulate gyrus, and pons, by applying ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Case-control differences were determined using multiple t-tests followed by correction with 10% false discovery rate.Results: We found urea concentrations to be substantively elevated in all nine regions, the average increase being 3-4-fold. Urea concentrations were remarkably consistent across regions in both cases and controls, with no clear distinction between regions heavily affected by neuronal loss in PDD compared to less severely affected areas. These urea elevations mirror those found in uraemic encephalopathy, where equivalent levels are generally considered to be pathogenic. These urea elevations also reflect those previously reported in AD and HD. Conclusions: Increased urea is a widespread metabolic perturbation in brain metabolism common to PDD, AD, and HD, at levels equal to those seen in uremic encephalopathy. This presents a novel pathogenic mechanism in PDD, which is shared with two other neurodegenerative diseases.

Abstract 241: Acetylomic and Metabolomic Alterations in Aged Hearts: Role for Silent Information Regulator (SIRT) 3

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jimmy Zhang ◽  
William R Urciuoli ◽  
Paul S Brookes ◽  
George A Porter ◽  
Sergiy M Nadtochiy
Keyword(s):  
Metabolic Pathways ◽  
Carbon Flux ◽  
Tca Cycle ◽  
Adult Group ◽  
Protein Levels ◽  
Mitochondrial Alterations ◽  
Age Related ◽  
Transport Chain ◽  
Tca Cycle Intermediates ◽  
Substantial Decline

Introduction: SIRT3 is a mitochondrial metabolic regulator, and a decline in function of SIRT3 may play a role in age-related mitochondrial alterations. The aim of this study was to investigate the possible down-regulation of SIRT3 activity in aged hearts, and to identify which metabolic pathways in aged hearts may be impaired due to SIRT3 dysfunction. Methods: Mitochondria were isolated from WT adult (7 mo.), SIRT3 -/- adult (7 mo.) and WT aged (18 mo.) hearts. Acetylated proteins in mitochondrial samples were identified using 2D gels and mass spectrometry. Metabolite concentrations and carbon fluxes through core metabolic pathways were determined using 13 C-labeled substrates and LC-MS/MS. Results: Mitochondrial acetylation patterns in the SIRT3 -/- adult group matched those found in the WT aged group; the level of acetylation was significantly higher than in WT adult. While the SIRT3 -/- samples exhibited zero SIRT3 protein content, no difference in SIRT3 protein level was seen between adult and aged WT hearts. Mechanistically, this suggests that alterations in mitochondrial acetylation during aging were not caused by lower SIRT3 protein levels, but rather by a lower SIRT3 enzymatic activity. Furthermore, aged myocardium exhibited 40% lower NAD + levels, which may underlie compromised SIRT3 activity. ATP levels were decreased in both SIRT3 -/- and WT aged hearts, suggesting possible defects in energy metabolism. Using metabolomics, we demonstrated that alterations of TCA cycle intermediates were similar in SIRT3 -/- and WT aged hearts (relative to WT adult), and included a substantial decline of carbon flux through α-ketoglutarate and malate. Furthermore, regulation of energy production might also be impaired at the level of the electron transport chain, where Complex I was significantly inhibited in both SIRT3 deficient and aged hearts. Conclusions: Collectively these data suggested that acetylomic and metabolomic fingerprints observed in SIRT3 -/- hearts were recapitulated in aged hearts.

Age-related change of the neuronal number in the human medial vestibular nucleus: A stereological investigation

2002 ◽  
Vol 11 (6) ◽  
pp. 357-363 ◽  
Author(s):  
Yong Tang ◽  
Ivan Lopez ◽  
Robert W. Baloh
Keyword(s):  
Correction Factor ◽  
Vestibular Nucleus ◽  
Neuronal Loss ◽  
Medial Vestibular Nucleus ◽  
Age At Death ◽  
Stereological Method ◽  
Age Related ◽  
Functional Implications ◽  
Neuronal Number ◽  
Stereological Investigation

An unbiased stereological method was used to assess the effect of aging on the number of neurons in the human medial vestibular nucleus. We studied 13 normal brainstem specimens (age at death from 40 to 93 years) that were part of a prior study that counted neuronal profiles and used a correction factor to estimate the number of neurons in the human vestibular nucleus. On average, we found 151 · 10 3 ( CV = 0.15) neurons in the medial vestibular nucleus, which is 18% significant decrease in the number of neurons with aging. This age-related neuronal loss in the vestibular nucleus could have important functional implications regarding the well-known deterioration in balance that occurs with aging.

Neurodegenerative Diseases

2016 ◽  
Author(s):  
Jeffrey L. Cummings ◽  
Jagan A. Pillai
Keyword(s):  
Clinical Trials ◽  
Neurodegenerative Diseases ◽  
Protein Misfolding ◽  
Scientific Progress ◽  
Neuronal Loss ◽  
Therapeutic Interventions ◽  
Growth Factor Signaling ◽  
Age Related ◽  
Human Ips Cells ◽  
Neuropsychiatric Manifestations

Neurodegenerative diseases (NDDs) are growing in frequency and represent a major threat to public health. Advances in scientific progress have made it clear that NDDs share many underlying processes, including shared intracellular mechanisms such as protein misfolding and aggregation, cell-to-cell prion-like spread, growth factor signaling abnormalities, RNA and DNA disturbances, glial cell changes, and neuronal loss. Transmitter deficits are shared across many types of disorders. Means of studying NDDs with human iPS cells and transgenic models are similar. The progression of NDDs through asymptomatic, prodromal, and manifest stages is shared across disorders. Clinical features of NDDs, including cognitive impairment, disease progression, age-related effects, terminal stages, neuropsychiatric manifestations, and functional disorders and disability, have many common elements. Clinical trials, biomarkers, brain imaging, and regulatory aspects of NDD can share information across NDDs. Disease-modifying and transmitter-based therapeutic interventions, clinical trials, and regulatory approaches to treatments for NDDs are also similar.

Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration

2006 ◽  
Vol 27 (7) ◽  
pp. 983-993 ◽  
Author(s):  
Janos Feher ◽  
Illes Kovacs ◽  
Marco Artico ◽  
Carlo Cavallotti ◽  
Antonio Papale ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Mitochondrial Alterations ◽  
Age Related

scholarly journals Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Maria H. Madeira ◽  
Raquel Boia ◽  
Paulo F. Santos ◽  
António F. Ambrósio ◽  
Ana R. Santiago
Keyword(s):  
Vision Loss ◽  
Neuronal Loss ◽  
Age Related Macular Degeneration ◽  
Therapeutic Interventions ◽  
Degenerative Diseases ◽  
Disease Etiology ◽  
Neurodegenerative Process ◽  
Age Related ◽  
Retinal Microglia ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy.

scholarly journals APPSW Transgenic Mice Develop Age-related Aβ Deposits and Neuropil Abnormalities, but no Neuronal Loss in CA1

1997 ◽  
Vol 56 (9) ◽  
pp. 965-973 ◽  
Author(s):  
MICHAEL C. IRIZARRY ◽  
MEGAN MCNAMARA ◽  
KERRI FEDORCHAK ◽  
KAREN HSIAO ◽  
BRADLEY T. HYMAN
Keyword(s):  
Transgenic Mice ◽  
Neuronal Loss ◽  
Age Related
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