scholarly journals Optimizing mitochondrial maintenance in extended neuronal projections

2021 ◽  
Vol 17 (6) ◽  
pp. e1009073
Author(s):  
Anamika Agrawal ◽  
Elena F. Koslover
Keyword(s):  
Steady State ◽  
Neurodegenerative Disorders ◽  
Quantitative Model ◽  
Organelle Transport ◽  
Optimal Distribution ◽  
Metabolic Demand ◽  
Mitochondrial Homeostasis ◽  
Fresh Material ◽  
New Material ◽  
High Metabolic Demand

Neurons rely on localized mitochondria to fulfill spatially heterogeneous metabolic demands. Mitochondrial aging occurs on timescales shorter than the neuronal lifespan, necessitating transport of fresh material from the soma. Maintaining an optimal distribution of healthy mitochondria requires an interplay between a stationary pool localized to sites of high metabolic demand and a motile pool capable of delivering new material. Interchange between these pools can occur via transient fusion / fission events or by halting and restarting entire mitochondria. Our quantitative model of neuronal mitostasis identifies key parameters that govern steady-state mitochondrial health at discrete locations. Very infrequent exchange between stationary and motile pools optimizes this system. Exchange via transient fusion allows for robust maintenance, which can be further improved by selective recycling through mitophagy. These results provide a framework for quantifying how perturbations in organelle transport and interactions affect mitochondrial homeostasis in neurons, a key aspect underlying many neurodegenerative disorders.

scholarly journals Optimizing Mitochondrial Maintenance in Extended Neuronal Projections

2020 ◽  
Author(s):  
Anamika Agrawal ◽  
Elena F. Koslover
Keyword(s):  
Steady State ◽  
Neurodegenerative Disorders ◽  
Quantitative Model ◽  
Organelle Transport ◽  
Optimal Distribution ◽  
Metabolic Demand ◽  
Mitochondrial Homeostasis ◽  
Fresh Material ◽  
New Material ◽  
High Metabolic Demand

Neurons rely on localized mitochondria to fulfill spatially heterogeneous metabolic demands. Mi-tochondrial aging occurs on timescales shorter than the neuronal lifespan, necessitating transport of fresh material from the soma. Maintaining an optimal distribution of healthy mitochondria requires an interplay between a stationary pool localized to sites of high metabolic demand and a motile pool capable of delivering new material. Interchange between these pools can occur via transient fusion / fission events or by halting and restarting entire mitochondria. Our quantitative model of neuronal mitostasis identifies key parameters that govern steady-state mitochondrial health at discrete locations. Very infrequent exchange between stationary and motile pools optimizes this system. Exchange via transient fusion allows for robust maintenance, which can be further improved by selective recycling through mitophagy. These results provide a framework for quantifying how perturbations in organelle transport and interactions affect mitochondrial homeostasis in neurons, an key aspect underlying many neurodegenerative disorders.

scholarly journals Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders

2021 ◽  
Author(s):  
Jan Spaas ◽  
Lieve van Veggel ◽  
Melissa Schepers ◽  
Assia Tiane ◽  
Jack van Horssen ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Treatment Strategies ◽  
Carbonyl Stress ◽  
Cell Type ◽  
Metabolic Demand ◽  
Oligodendrocyte Precursor ◽  
Underlying Mechanisms ◽  
Cellular Defence ◽  
High Metabolic Demand

AbstractOligodendrocyte precursor cells (OPCs) account for 5% of the resident parenchymal central nervous system glial cells. OPCs are not only a back-up for the loss of oligodendrocytes that occurs due to brain injury or inflammation-induced demyelination (remyelination) but are also pivotal in plastic processes such as learning and memory (adaptive myelination). OPC differentiation into mature myelinating oligodendrocytes is controlled by a complex transcriptional network and depends on high metabolic and mitochondrial demand. Mounting evidence shows that OPC dysfunction, culminating in the lack of OPC differentiation, mediates the progression of neurodegenerative disorders such as multiple sclerosis, Alzheimer’s disease and Parkinson’s disease. Importantly, neurodegeneration is characterised by oxidative and carbonyl stress, which may primarily affect OPC plasticity due to the high metabolic demand and a limited antioxidant capacity associated with this cell type. The underlying mechanisms of how oxidative/carbonyl stress disrupt OPC differentiation remain enigmatic and a focus of current research efforts. This review proposes a role for oxidative/carbonyl stress in interfering with the transcriptional and metabolic changes required for OPC differentiation. In particular, oligodendrocyte (epi)genetics, cellular defence and repair responses, mitochondrial signalling and respiration, and lipid metabolism represent key mechanisms how oxidative/carbonyl stress may hamper OPC differentiation in neurodegenerative disorders. Understanding how oxidative/carbonyl stress impacts OPC function may pave the way for future OPC-targeted treatment strategies in neurodegenerative disorders.

scholarly journals Heat Shock Protein 90 as Therapeutic Target for CVDs and Heart Ageing

2022 ◽  
Vol 23 (2) ◽  
pp. 649
Author(s):  
Siarhei A. Dabravolski ◽  
Vasily N. Sukhorukov ◽  
Vladislav A. Kalmykov ◽  
Nikolay A. Orekhov ◽  
Andrey V. Grechko ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Molecular Chaperones ◽  
Heat Shock Protein 90 ◽  
Misfolded Proteins ◽  
Heart Cells ◽  
Metabolic Demand ◽  
Heart Protection ◽  
High Metabolic Demand

Cardiovascular diseases (CVDs) are the leading cause of death globally, representing approximately 32% of all deaths worldwide. Molecular chaperones are involved in heart protection against stresses and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins, thus supporting the high metabolic demand of the heart cells. Heat shock protein 90 (HSP90) is one of the main cardioprotective chaperones, represented by cytosolic HSP90a and HSP90b, mitochondrial TRAP1 and ER-localised Grp94 isoforms. Currently, the main way to study the functional role of HSPs is the application of HSP inhibitors, which could have a different way of action. In this review, we discussed the recently investigated role of HSP90 proteins in cardioprotection, atherosclerosis, CVDs development and the involvements of HSP90 clients in the activation of different molecular pathways and signalling mechanisms, related to heart ageing.

STATUS OF OXIDANT (MDA) ANTIOXIDANT (SOD) IN FIRST AND THIRD TRIMESTER OF NORMAL PREGNANCY IN TERTIARY CENTER OF CENTRAL INDIA

2021 ◽  
pp. 12-14
Author(s):  
Tamrakar Seema ◽  
Sachdeva Payasvi ◽  
Tripathi Rashmi
Keyword(s):  
Oxidative Stress ◽  
Pregnant Women ◽  
Central India ◽  
Normal Pregnancy ◽  
Metabolic Demand ◽  
Third Trimester ◽  
Dynamic Changes ◽  
Tertiary Center ◽  
Antioxidant Supplements ◽  
High Metabolic Demand

INTRODUCTION: Pregnancy is associated with high metabolic demand and increased demand for tissue oxygen. Consequently increased production of reactive oxygen species. This leads in increased oxidative stress and decreases antioxidant status during gestational age of normal pregnant women. Aim: Aim of this study was to evaluate the level of oxidant and antioxidant in 1st and 3rd trimester of normal pregnant women. MATERIAL AND METHODS: The present study included total 150 cases attended ANC Clinic at the department of Gynae LNMC & J K Hospital was screened for the study. Level of MDA was estimated by Jean et al and SOD was Marklund and Marklund. RESULTS: Findings were, that there was signicantly increase in Malondialdehyde levels (p<0.001) and signicantly decrease in superoxide dismutase activities (P<0.001) in 1st and 3rd trimester of normal pregnant women. Conclusion: present study concludes that there was difference in oxidative status due to dynamic changes. During pregnancy oxidative stress is increased and antioxidant decreased that can be fatal to the health of the mother and the fetus. Therefore antioxidant supplements should be prescribed in early pregnancy to prevent the overwhelming of oxidative stress in pregnant females.

The Lex Irnitana and Procedure in the Civil Courts

1991 ◽  
Vol 81 ◽  
pp. 74-90 ◽  
Author(s):  
Alan Rodger
Keyword(s):  
Legal System ◽  
First Century ◽  
Roman World ◽  
Fresh Material ◽  
New Material ◽  
Civil Courts

The procedural rules of civil courts stimulate interest among few except the lawyers who practise in them. The procedures of the courts of the Roman world may therefore not seem an enticing topic. But procedure lies at the heart of any legal system and the Roman legal system is no exception. So when the discovery of the Lex Irnitana brought us fresh material about the jurisdiction and procedure of the local magistrates and courts at Irni, it added greatly to our understanding of one of the central institutions of the first-century Roman world. But the information is not always easy to interpret. The purpose of this article is first to try to solve an apparent mystery in Chapter 90 of the Lex and then to use the new material to fill out our picture of procedure in this period. In this way it is hoped to contribute to a fuller understanding of the Lex Irnitana as a whole.

scholarly journals Stimulus-evoked changes in cerebral vessel diameter: A study in healthy humans

2017 ◽  
Vol 38 (3) ◽  
pp. 528-539 ◽  
Author(s):  
Alexandre Bizeau ◽  
Guillaume Gilbert ◽  
Michaël Bernier ◽  
Minh Tung Huynh ◽  
Christian Bocti ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Visual Stimulation ◽  
Occipital Lobe ◽  
Vessel Diameter ◽  
Metabolic Demand ◽  
Cerebral Vessel ◽  
Non Invasive ◽  
Healthy Humans ◽  
Induced Changes ◽  
High Metabolic Demand

The high metabolic demand of neuronal tissue, coupled with its relatively low energy storage capacity, requires that increases in neuronal activation are quickly matched with increased blood flow to ensure efficient supply of oxygen and nutrients to the tissue. For this to occur, dilation of nearby arterioles must be coordinated with the dilation of larger upstream feeding arteries. As it stands, the exact spatial extent of such dilation in humans is unknown. Using non-invasive time-of-flight magnetic resonance angiography in healthy participants, we developed an automatic methodology for reconstructing cerebral arterial vessels and quantifying their diameter on a voxel-by-voxel basis. Specifically, we isolated the posterior cerebral artery (PCA) supplying each occipital lobe and quantified its vasodilation induced by visual stimulation. Stimulus-induced changes were strongest (∼30%) near primary visual cortex and progressively decreased in a non-linear fashion as a function of distance. Surprisingly, weak – albeit significant – changes (∼2%) were observed ∼70 mm from the visual cortex. This demonstrates that visual stimulation modulates vascular tone along the bulk of the PCA segment, and thus may have important implications for our understanding of functional hyperemia in healthy and diseased states.

scholarly journals Apoplexy of pituitary adenomas: the perfect storm

2015 ◽  
Vol 122 (6) ◽  
pp. 1444-1449 ◽  
Author(s):  
Edward H. Oldfield ◽  
Marsha J. Merrill
Keyword(s):  
Pituitary Adenomas ◽  
Insulin Infusion ◽  
Pituitary Apoplexy ◽  
Pituitary Tumors ◽  
Tissue Perfusion ◽  
Acute Ischemia ◽  
Metabolic Demand ◽  
Releasing Factors ◽  
Perfect Storm ◽  
High Metabolic Demand

OBJECT Pituitary adenomas occasionally undergo infarction, apoplexy, which often destroys much of the tumor. It is well known that apoplexy can be precipitated by several acute factors, including cardiac surgery, other types of surgery, trauma, insulin infusion, and stimulation with administration of hypothalamic releasing factors. METHODS The prior focus on mechanisms underlying pituitary apoplexy has been on these acute events. Less attention has been given to the endogenous features of pituitary tumors that make them susceptible to spontaneous infarction, despite that most pituitary apoplexy occurs in the absence of a recognized precipitating event. The authors examine intrinsic features of pituitary adenomas that render them vulnerable to apoplexy—features such as high metabolic demand, paucity of angiogenesis, and sparse vascularity, qualities that have previously not been linked with apoplexy—and argue that it is these features of adenomas that underlie their susceptibility to spontaneous infarction. The sensitivity of freshly cultured pituitary adenomas to hypoglycemia is assessed. RESULTS Adenomas have high metabolic demand, limited angiogenesis, and reduced vessel density compared with the normal gland. Pituitary adenoma cells do not survive in the presence of reduced or absent concentrations of glucose. CONCLUSIONS The authors propose that the frequent ischemic infarction of pituitary adenomas is the product of intrinsic features of these tumors. These endogenous qualities create a tenuous balance between high metabolic demand and marginal tissue perfusion. Thus, the tumor is vulnerable to spontaneous infarction or to acute ischemia by any event that acutely alters the balance between tumor perfusion and tumor metabolism, events such as acute systemic hypotension, abruptly decreased supply of nutrients, hypoglycemia with insulin administration, or increase in the tumor's metabolic demand due to administration of hypothalamic releasing factors. It may be possible to take advantage of these intrinsic features of pituitary adenomas by using aspects of this vulnerability for development of new approaches for treatment.

scholarly journals Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl-CoA dehydrogenase (MCAD)-deficient mice

Hepatology ◽  
2008 ◽  
Vol 47 (6) ◽  
pp. 1894-1904 ◽  
Author(s):  
Hilde Herrema ◽  
Terry G. J. Derks ◽  
Theo H. van Dijk ◽  
Vincent W. Bloks ◽  
Albert Gerding ◽  
...  
Keyword(s):  
Metabolic Demand ◽  
Medium Chain ◽  
Chain Acyl ◽  
Deficient Mice ◽  
High Metabolic Demand
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