scholarly journals Age-Induced Loss of Mossy Fibre Synapses on CA3 Thorns in the CA3 Stratum Lucidum

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Bunmi Ojo ◽  
Heather Davies ◽  
Payam Rezaie ◽  
Paul Gabbott ◽  
Francis Colyer ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Synaptic Connection ◽  
Mossy Fibre ◽  
Synaptic Density ◽  
Cellular Processes ◽  
Unbiased Stereology ◽  
Microvascular Changes ◽  
Age Related ◽  
Stratum Lucidum ◽  
Serial Electron Microscopy

Advanced ageing is associated with hippocampal deterioration and mild cognitive decline. The hippocampal subregion CA3 stratum lucidum (CA3-SL) receives neuronal inputs from the giant mossy fibre boutons of the dentate gyrus, but relatively little is known about the integrity of this synaptic connection with ageing. Using serial electron microscopy and unbiased stereology, we examined age-related changes in mossy fibre synapses on CA3 thorny excrescences within the CA3-SL of young adults (4-month-old), middle-aged (12-month-old), and old-aged (28-month-old) Wistar rats. Our data show that while there is an increase in CA3 volume with ageing, there is a significant (40–45%) reduction in synaptic density within the CA3-SL of 12- and 28-month-old animals compared with 4-month-old animals. We also present preliminary data showing that the CA3 neuropil in advanced ageing was conspicuously full of lipofuscin and phagolysosome positive, activated microglial cellular processes, and altered perivascular pathology. These data suggest that synaptic density in the CA3-SL is significantly impaired in ageing, accompanied by underlying prominent ultrastructural glial and microvascular changes.

Renal Cortical Slices: An In Vitro Model for Kidney Metabolism and Toxicity

1992 ◽  
Vol 20 (1) ◽  
pp. 71-76
Author(s):  
Andrea Trevisan ◽  
Stefano Maso ◽  
Paola Meneghetti
Keyword(s):  
Wistar Rats ◽  
Reduced Glutathione ◽  
Organic Anion ◽  
Cortical Slice ◽  
Lactate Dehydrogenase Release ◽  
Age Related ◽  
Renal Cortical Slice ◽  
Male Wistar Rats ◽  
Vitro Model

The in vitro renal cortical slice model was used to study: 1) the effects on the kidney of some haloalkanes and haloalkenes using 3-month-old male Wistar rats; 2) influence of age and sex on renal cortical slice indices in non-treated rats; and 3) effects of 1,2-dichloropropane on the slices after pretreatment of 3-month-old male Wistar rats with DL-butathionine-[S,R]-sulphoximine. The most nephrotoxic chemical used was 1,3-dichloropropene, which caused a total depletion in the levels of reduced glutathione, a high peroxidation of lipid (about three thousand-fold with respect to control), a significant release of tubular enzymes into the medium, and loss of organic anion ( p-aminohippurate) accumulation. All the chemicals affected the cytosol more than the brush border. The most remarkable age-related differences in the untreated slices were the progressive decrease of reduced glutathione (p<0.05 from three months of age), and an increase in lactate dehydrogenase release into the medium (p<0.05 from six months of age). By contrast, sex differences were slight. The ‘treatment with 1,2-dichloropropane of slices prepared from rats pretreated with DL-butathionine-[S,R]-sulphoximine significantly increased the depletion of glutathione content (p<0.05) and malondialdehyde release in the medium (p<0.001) caused by the solvent alone.

scholarly journals Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Swapnil Gupta ◽  
Panpan You ◽  
Tanima SenGupta ◽  
Hilde Nilsen ◽  
Kulbhushan Sharma
Keyword(s):  
Dna Repair ◽  
Neurodegenerative Diseases ◽  
3D Models ◽  
Model Systems ◽  
Spinocerebellar Ataxias ◽  
C Elegans ◽  
Cellular Processes ◽  
Age Related ◽  
Damage Response ◽  
Lateral Sclerosis

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

scholarly journals NAD+Metabolism in Aging and Cancer

2019 ◽  
Vol 3 (1) ◽  
pp. 105-130 ◽  
Author(s):  
Tyler G. Demarest ◽  
Mansi Babbar ◽  
Mustafa N. Okur ◽  
Xiuli Dan ◽  
Deborah L. Croteau ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Accelerated Aging ◽  
Cancer Therapies ◽  
Nad Metabolism ◽  
Cellular Processes ◽  
Cancer Pathogenesis ◽  
Nicotinamide Mononucleotide ◽  
Age Related

Aging is a major risk factor for many types of cancer, and the molecular mechanisms implicated in aging, progeria syndromes, and cancer pathogenesis display considerable similarities. Maintaining redox homeostasis, efficient signal transduction, and mitochondrial metabolism is essential for genome integrity and for preventing progression to cellular senescence or tumorigenesis. NAD+is a central signaling molecule involved in these and other cellular processes implicated in age-related diseases and cancer. Growing evidence implicates NAD+decline as a major feature of accelerated aging progeria syndromes and normal aging. Administration of NAD+precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) offer promising therapeutic strategies to improve health, progeria comorbidities, and cancer therapies. This review summarizes insights from the study of aging and progeria syndromes and discusses the implications and therapeutic potential of the underlying molecular mechanisms involved in aging and how they may contribute to tumorigenesis.

scholarly journals Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

2020 ◽  
Vol 21 (7) ◽  
pp. 2576 ◽  
Author(s):  
Sandra Buratta ◽  
Brunella Tancini ◽  
Krizia Sagini ◽  
Federica Delo ◽  
Elisabetta Chiaradia ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cell Communication ◽  
Lysosomal Storage ◽  
Cellular Processes ◽  
Age Related ◽  
Extracellular Release ◽  
A Cell ◽  
Endosomal System

Beyond the consolidated role in degrading and recycling cellular waste, the autophagic- and endo-lysosomal systems play a crucial role in extracellular release pathways. Lysosomal exocytosis is a process leading to the secretion of lysosomal content upon lysosome fusion with plasma membrane and is an important mechanism of cellular clearance, necessary to maintain cell fitness. Exosomes are a class of extracellular vesicles originating from the inward budding of the membrane of late endosomes, which may not fuse with lysosomes but be released extracellularly upon exocytosis. In addition to garbage disposal tools, they are now considered a cell-to-cell communication mechanism. Autophagy is a cellular process leading to sequestration of cytosolic cargoes for their degradation within lysosomes. However, the autophagic machinery is also involved in unconventional protein secretion and autophagy-dependent secretion, which are fundamental mechanisms for toxic protein disposal, immune signalling and pathogen surveillance. These cellular processes underline the crosstalk between the autophagic and the endosomal system and indicate an intersection between degradative and secretory functions. Further, they suggest that the molecular mechanisms underlying fusion, either with lysosomes or plasma membrane, are key determinants to maintain cell homeostasis upon stressing stimuli. When they fail, the accumulation of undigested substrates leads to pathological consequences, as indicated by the involvement of autophagic and lysosomal alteration in human diseases, namely lysosomal storage disorders, age-related neurodegenerative diseases and cancer. In this paper, we reviewed the current knowledge on the functional role of extracellular release pathways involving lysosomes and the autophagic- and endo-lysosomal systems, evaluating their implication in health and disease.

scholarly journals Altered Nuclear Functions in Progeroid Syndromes: a Paradigm for Aging Research

2009 ◽  
Vol 9 ◽  
pp. 1449-1462 ◽  
Author(s):  
Baomin Li ◽  
Sonali Jog ◽  
Jose Candelario ◽  
Sita Reddy ◽  
Lucio Comai
Keyword(s):  
Werner Syndrome ◽  
Accelerated Aging ◽  
Natural Aging ◽  
Aging Research ◽  
Cellular Processes ◽  
Functional Connections ◽  
Age Related ◽  
Progeroid Syndromes ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Syndromes of accelerated aging could provide an entry point for identifying and dissecting the cellular pathways that are involved in the development of age-related pathologies in the general population. However, their usefulness for aging research has been controversial, as it has been argued that these diseases do not faithfully reflect the process of natural aging. Here we review recent findings on the molecular basis of two progeroid diseases, Werner syndrome (WS) and Hutchinson-Gilford progeria syndrome (HGPS), and highlight functional connections to cellular processes that may contribute to normal aging.

Effects of maturation on adrenergic neurotransmission in ovine cerebral arteries

1999 ◽  
Vol 277 (4) ◽  
pp. R931-R937 ◽  
Author(s):  
William J. Pearce ◽  
Sue P. Duckles ◽  
John Buchholz
Keyword(s):  
Cerebral Arteries ◽  
Age Groups ◽  
Peptidergic Neurons ◽  
Synaptic Density ◽  
Vasoactive Substances ◽  
Age Related ◽  
Middle Cerebral Arteries ◽  
Adrenergic Neurotransmission ◽  
Fractional Release ◽  
Two Age Groups

The present studies examine the hypothesis that multiple adrenergic neuroeffector mechanisms are not fully developed in fetal, compared with adult, ovine middle cerebral arteries. In arteries denuded of endothelium and pretreated with 1 μM atropine to block involvement of muscarinic receptors, 10 μM capsaicin to deplete sensory peptidergic neurons, and 10 μM nitro-l-arginine methyl ester (l-NAME) to block possible influences from nitric oxidergic innervation, transmural stimulation at 16 Hz increased contractile tensions to 9.5 ± 3.7% ( n = 6) of the potassium maximum in adult arteries. Corresponding values in fetal arteries, however, were significantly less and averaged only 1.1 ± 0.6% ( n =10). However, postsynaptic sensitivity to norepinephrine (NE) was similar in the two age groups; NE pD2 values (−log EC50) averaged 6.11 ± 0.12 ( n = 6) and 6.33 ± 0.09 M ( n = 9) in fetal and adult arteries, respectively. Similarly, NE content measured via HPLC was also similar in the two age groups and averaged 32.4 ± 5.0 ( n = 17) and 32.5 ± 3.9 ng/ng wet wt ( n = 13) in fetal and adult middle cerebral arteries, respectively. In contrast, stimulation-induced NE release was greater in fetal than in adult arteries, whether calculated as total mass released [883 ± 184 ( n = 17) vs. 416 ± 106 pg NE/mg wet wt ( n = 13)] or as fractional release [51.1 ± 5.3 ( n = 17) vs. 22.8 ± 3.8 pg/pg NE content per pulse × 10−6]. Measured as an index of synaptic density, neuronal cocaine-sensitive NE uptake was similar in fetal and adult arteries [1.55 ± 0.40 ( n = 10) and 1.84 ± 0.51 pmol/mg wet wt ( n = 7), respectively]. Overall, age-related differences in postsynaptic sensitivity to NE, NE release, and NE uptake capacity cannot explain the corresponding age-related differences in response to stimulation. The data thus suggest that total synaptic volume and cleft width, in particular, are probably greater and/or that adrenergic corelease of vasoactive substances other than NE is altered in fetal compared with adult middle cerebral arteries.

Sign in / Sign up

Export Citation Format

Share Document