scholarly journals Energy Metabolism Decline in the Aging Brain; Pathogenesis of Neurodegenerative Disorders

2020 ◽  
Author(s):  
Janusz Błaszczyk
Keyword(s):  
Energy Metabolism ◽  
Neurodegenerative Diseases ◽  
Krebs Cycle ◽  
Brain Structures ◽  
The Elderly ◽  
Review Article ◽  
Aging Brain ◽  
Salvage Pathway ◽  
Atp Production ◽  
The Brain

A growing body of evidence indicates that aging of the brain is strictly related to the decline of energy metabolism. In particular, in older adults, the neuronal metabolism of glucose declines steadily resulting in a growing deficit of ATP production. The decline is evoked by deficient NAD recovery in the salvage pathway and subsequent impairment of the Krebs cycle. NAD deficit impairs also the activity of NAD-dependent enzymes. All these open vicious circles of neurodegeneration and neuronal death. Some brain structures are particularly prone to aging and neurodegeneration. These are pathological foci of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This review article summarizes the impacts and mutual relationships between metabolic processes both on neuronal and brain levels. It also provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.

scholarly journals Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders

Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 450
Author(s):  
Janusz Wiesław Błaszczyk
Keyword(s):  
Energy Metabolism ◽  
Neurodegenerative Disorders ◽  
Clinical Symptoms ◽  
Neuronal Degeneration ◽  
Brain Structures ◽  
Aging Brain ◽  
Atp Production ◽  
Sequence Of Events ◽  
Age Related ◽  
The Brain

There is a growing body of evidencethat indicates that the aging of the brain results from the decline of energy metabolism. In particular, the neuronal metabolism of glucose declines steadily, resulting in a growing deficit of adenosine triphosphate (ATP) production—which, in turn, limits glucose access. This vicious circle of energy metabolism at the cellular level is evoked by a rising deficiency of nicotinamide adenine dinucleotide (NAD) in the mitochondrial salvage pathway and subsequent impairment of the Krebs cycle. A decreasing NAD level also impoverishes the activity of NAD-dependent enzymes that augments genetic errors and initiate processes of neuronal degeneration and death.This sequence of events is characteristic of several brain structures in which neurons have the highest energy metabolism. Neurons of the cerebral cortex and basal ganglia with long unmyelinated axons and these with numerous synaptic junctions are particularly prone to senescence and neurodegeneration. Unfortunately, functional deficits of neurodegeneration are initially well-compensated, therefore, clinical symptoms are recognized too late when the damages to the brain structures are already irreversible. Therefore, future treatment strategies in neurodegenerative disorders should focus on energy metabolism and compensation age-related NAD deficit in neurons. This review summarizes the complex interrelationships between metabolic processes on the systemic and cellular levels and provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.

scholarly journals The Biology and Pathobiology of Glutamatergic, Cholinergic, and Dopaminergic Signaling in the Aging Brain

2021 ◽  
Vol 13 ◽  
Author(s):  
Anna Gasiorowska ◽  
Malgorzata Wydrych ◽  
Patrycja Drapich ◽  
Maciej Zadrozny ◽  
Marta Steczkowska ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Experimental Studies ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
The Elderly ◽  
Aging Brain ◽  
Detailed Knowledge ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
The Brain

The elderly population is growing worldwide, with important health and socioeconomic implications. Clinical and experimental studies on aging have uncovered numerous changes in the brain, such as decreased neurogenesis, increased synaptic defects, greater metabolic stress, and enhanced inflammation. These changes are associated with cognitive decline and neurobehavioral deficits. Although aging is not a disease, it is a significant risk factor for functional worsening, affective impairment, disease exaggeration, dementia, and general disease susceptibility. Conversely, life events related to mental stress and trauma can also lead to accelerated age-associated disorders and dementia. Here, we review human studies and studies on mice and rats, such as those modeling human neurodegenerative diseases, that have helped elucidate (1) the dynamics and mechanisms underlying the biological and pathological aging of the main projecting systems in the brain (glutamatergic, cholinergic, and dopaminergic) and (2) the effect of defective glutamatergic, cholinergic, and dopaminergic projection on disabilities associated with aging and neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Detailed knowledge of the mechanisms of age-related diseases can be an important element in the development of effective ways of treatment. In this context, we briefly analyze which adverse changes associated with neurodegenerative diseases in the cholinergic, glutaminergic and dopaminergic systems could be targeted by therapeutic strategies developed as a result of our better understanding of these damaging mechanisms.

Aging of Brain Related with Mitochondrial Dysfunctions

2020 ◽  
Vol 21 ◽  
Author(s):  
Vipin Dhote ◽  
Prem Samundre ◽  
Aditya Ganeshpurkar ◽  
Aman Upaganlawar
Keyword(s):  
Neurodegenerative Diseases ◽  
Psychiatric Symptoms ◽  
Neuronal Damage ◽  
The Elderly ◽  
Environmental Chemicals ◽  
Aging Brain ◽  
Mitochondrial Dysfunctions ◽  
Mitochondrial Functions ◽  
Key Issues ◽  
The Brain

Abstract:: Advancing age presents a major challenge for the elderly population in terms of quality of life. The risk of cognitive impairment, motor in-coordination, and behavioral inconsistency due to neuronal damage is relatively higher in aging individuals of society. The brain, through its structural and functional integrity, regulates vital physiological events; however, the susceptibility of the brain to aging-related disturbances signal the onset of neurodegenerative diseases. Mitochondrial dysfunctions impair bioenergetic mechanism, synaptic plasticity, and calcium homeostasis in the brain, thus sufficiently implying mitochondria as a prime causal factor in accelerating aging-related neurodegeneration. We reviewed the fundamental functions of mitochondria in a healthy brain and aimed to address the key issues in aging-related diseases by asking: 1) What goes wrong with mitochondria in the aging brain? 2) What are the implications of mitochondrial damage on motor functions and psychiatric symptoms? 3) How environmental chemicals and metabolic morbidities affect mitochondrial functions? Further, we share insight on opportunities and pitfalls in drug discovery approaches targeting mitochondria to slow down the progression of aging and related neurodegenerative diseases.

scholarly journals Regulatory Roles of Bone in Neurodegenerative Diseases

2020 ◽  
Vol 12 ◽  
Author(s):  
Zhengran Yu ◽  
Zemin Ling ◽  
Lin Lu ◽  
Jin Zhao ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
The Elderly ◽  
Lymphoid Organ ◽  
The Body ◽  
Hematopoietic Stem ◽  
Brain Functions ◽  
And Function ◽  
The Impact ◽  
The Brain

Osteoporosis and neurodegenerative diseases are two kinds of common disorders of the elderly, which often co-occur. Previous studies have shown the skeletal and central nervous systems are closely related to pathophysiology. As the main structural scaffold of the body, the bone is also a reservoir for stem cells, a primary lymphoid organ, and an important endocrine organ. It can interact with the brain through various bone-derived cells, mostly the mesenchymal and hematopoietic stem cells (HSCs). The bone marrow is also a place for generating immune cells, which could greatly influence brain functions. Finally, the proteins secreted by bones (osteokines) also play important roles in the growth and function of the brain. This article reviews the latest research studying the impact of bone-derived cells, bone-controlled immune system, and bone-secreted proteins on the brain, and evaluates how these factors are implicated in the progress of neurodegenerative diseases and their potential use in the diagnosis and treatment of these diseases.

scholarly journals Energy-modulating vitamins – a new combinatorial therapy prevents cancer cachexia in rat mammary carcinoma

2005 ◽  
Vol 93 (6) ◽  
pp. 901-909 ◽  
Author(s):  
Selvanathan Saravana Perumal ◽  
Palanivelu Shanthi ◽  
Panchanadham Sachdanandam
Keyword(s):  
Body Weight ◽  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Oral Administration ◽  
Cancer Cells ◽  
Mammary Carcinoma ◽  
Cancer Cachexia ◽  
Krebs Cycle ◽  
Mitochondrial Enzymes ◽  
Atp Production

Mitochondria are the major intracellular organelles producing ATP molecules via the electron transport chain. Cancer cells have a deviant energy metabolism, and a high rate of glycolysis is related to a high degree of dedifferentiation and proliferation. The overall net ATP production is diminished with cancer, which ultimately leads to cancer cachexia. The present study was designed to investigate the altered energy metabolism in cancer cells and to enhance ATP production in the normal host cell metabolism by enhancing the activities of mitochondrial enzymes, using energy-modulating vitamins, and thus prevent cancer cachexia. Female Sprague–Dawley rats were selected for the experimental study. Mammary carcinoma was induced by the oral administration of 7,12-dimethylbenz[a]anthracene (25 mg/kg body weight), and treatment was started by the oral administration of the energy-modulating vitamins riboflavin (45 mg/kg body weight per d), niacin (100 mg/kg body weight per d) and coenzyme Q10(40 mg/kg body weight per d) for 28 d. Mitochondria were isolated from the mammary gland and liver of all four groups, and the Krebs cycle and oxidative phosphorylation enzymes were assayed. In mammary carcinoma-bearing animals, the activities of the Krebs cycle and oxidative phosphorylation enzymes were significantly decreased. These activities were restored to a greater extent in animals treated with energy-modulating vitamins. From these experimental results, one may hypothesize that the combination therapy of energy-modulating vitamins could be of major therapeutic value in breast cancer.

How Musical Activity Shapes Memory

2020 ◽  
Vol 31 (2) ◽  
pp. 55-61 ◽  
Author(s):  
Martina Hoffmann ◽  
Christoph J. Ploner ◽  
Alexander Schmidt
Keyword(s):  
Elderly Population ◽  
Brain Plasticity ◽  
Brain Structures ◽  
The Elderly ◽  
Memory Capacity ◽  
Musical Instrument ◽  
Brain Areas ◽  
Memory Functioning ◽  
Musical Activity ◽  
The Brain

Abstract. Musical activity has been found to drive plasticity in brain areas involved in the process of playing a musical instrument. The present article reviews how musical activity influences the brain structures involved in memory and how it impacts on memory functioning memory functioning. Musical activity appears to be associated with better memory capacity across the lifespan. Importantly, training-induced effects are not restricted to childhood, but can occur even in the elderly population. We conclude by outlining how musical activity, both on the receptive and active level, can be beneficial to patients suffering from memory disorders, inducing brain plasticity and memory improvement.

scholarly journals Astrocytes as Key Regulators of Brain Energy Metabolism: New Therapeutic Perspectives

2022 ◽  
Vol 12 ◽  
Author(s):  
Elidie Beard ◽  
Sylvain Lengacher ◽  
Sara Dias ◽  
Pierre J. Magistretti ◽  
Charles Finsterwald
Keyword(s):  
Energy Metabolism ◽  
Neurodegenerative Diseases ◽  
Critical Role ◽  
Functional Brain Imaging ◽  
Brain Energy Metabolism ◽  
Lactate Shuttle ◽  
Lactate Release ◽  
Brain Functions ◽  
The Brain ◽  
Brain Energy

Astrocytes play key roles in the regulation of brain energy metabolism, which has a major impact on brain functions, including memory, neuroprotection, resistance to oxidative stress and homeostatic tone. Energy demands of the brain are very large, as they continuously account for 20–25% of the whole body’s energy consumption. Energy supply of the brain is tightly linked to neuronal activity, providing the origin of the signals detected by the widely used functional brain imaging techniques such as functional magnetic resonance imaging and positron emission tomography. In particular, neuroenergetic coupling is regulated by astrocytes through glutamate uptake that triggers astrocytic aerobic glycolysis and leads to glucose uptake and lactate release, a mechanism known as the Astrocyte Neuron Lactate Shuttle. Other neurotransmitters such as noradrenaline and Vasoactive Intestinal Peptide mobilize glycogen, the reserve for glucose exclusively localized in astrocytes, also resulting in lactate release. Lactate is then transferred to neurons where it is used, after conversion to pyruvate, as a rapid energy substrate, and also as a signal that modulates neuronal excitability, homeostasis, and the expression of survival and plasticity genes. Importantly, glycolysis in astrocytes and more generally cerebral glucose metabolism progressively deteriorate in aging and age-associated neurodegenerative diseases such as Alzheimer’s disease. This decreased glycolysis actually represents a common feature of several neurological pathologies. Here, we review the critical role of astrocytes in the regulation of brain energy metabolism, and how dysregulation of astrocyte-mediated metabolic pathways is involved in brain hypometabolism. Further, we summarize recent efforts at preclinical and clinical stages to target brain hypometabolism for the development of new therapeutic interventions in age-related neurodegenerative diseases.

scholarly journals Curcumae Radix Extract Reduces Beta-Amyloid (Αβ) and Tau Protein Through Increased Mitochondrial Respiration

2021 ◽  
Author(s):  
Seong lae Jo ◽  
Hyun Yang ◽  
Jun H. Heo ◽  
Sang R. Lee ◽  
Hye Won Lee ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Energy Metabolism ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Respiration ◽  
Metabolic Flux ◽  
Tca Cycle ◽  
Basal Respiration ◽  
Atp Production ◽  
Inflammatory Conditions ◽  
Brain Tumor Cells

Abstract Background: Neurodegenerative diseases are increasingly being studied owing to the increasing proportion of the aging population. Several potential compounds have been studied to prevent neurodegenerative diseases, one of which is Curcumae Radix that is known to be beneficial for inflammatory conditions, metabolic syndrome, and various types of pain. However, it is not well studied and its influence on energy metabolism in neurodegenerative diseases is unclear. We focused on the relationship between neurodegenerative diseases and energy metabolism through Curcumae Radix extract in an animal model. Methods: Mice were treated with Curcumae Radix extract for 5 weeks orally 5 times in a week (50 mg/kg body weight). Murine delayed brain tumor (DBT) cells were supplemented with Curcumae Radix extract. We monitored the neurodegenerative makers and metabolic indicators using Western blotting and qRT-PCR and then assessed the cellular glycolysis and mitochondrial respiration through metabolic flux assay.Results: Low expression levels of Alzheimer’s disease-related markers were observed after treatment with Curcumae Radix extract. It was determined through the pAMPK/AMPK ratio that the ATP state was sufficient in the cerebrum and brain tumor cells. With this, an increase in glycolysis would be expected as glucose is the main energy source of the brain. However, glycolysis-related genes and the extracellular acidification rate showed that glycolysis decreased. Despite this, basal respiration and ATP production through mitochondrial respiration and increased TCA cycle and OXPHOS-related genes were observed in the Curcumae Radix group. Conclusions: In neurodegenerative diseases involving mitochondrial dysfunction, Curcumae Radix may act as a metabolic modulator of brain health to treat and prevent these diseases.

Glutamine and glucose metabolism in thymocytes from normal and spontaneously diabetic BB rats

1991 ◽  
Vol 69 (12) ◽  
pp. 801-808 ◽  
Author(s):  
Guoyao Wu ◽  
Catherine J. Field ◽  
Errol B. Marliss
Keyword(s):  
Energy Metabolism ◽  
Krebs Cycle ◽  
Major Product ◽  
Lymphoid Organs ◽  
Glutamine Metabolism ◽  
Potential Production ◽  
Atp Production ◽  
Bb Rats ◽  
Oxidation Of Glucose ◽  
Diabetic Syndrome

Metabolism of glutamine and glucose was studied in thymocytes from normal rats and BB rats with the spontaneous autoimmune diabetic syndrome to assess their potential roles as fuels. The major measured products from glucose were lactate and, to a lesser extent, CO2, and pyruvate. Glutamine had no effect on the rates of their production from glucose. Glutamine was metabolized to ammonia, aspartate, glutamate, and CO2, with aspartate being the major product of carbons from glutamine in the absence of glucose. Glucose markedly decreased the formation of ammonia, aspartate, and CO2 from glutamine, but increased that of glutamate, with an overall decrease in glutamine utilization by 55%. More glutamate than aspartate was produced from glutamine in the presence of glucose. The potential production of ATP from glucose was similar to that when glutamine was present alone. However, glucose markedly decreased production of ATP from glutamine, but not vice versa. This resulted in ATP production from glucose being 2.5 times that from glutamine when both substrates were present. The oxidation of glucose to CO2 via the Krebs cycle accounts for 75–80% of glucose-derived ATP production. Cellular ATP levels markedly decreased in the absence of exogenous substrates, but were constant throughout a 2-h incubation in the presence of glutamine, glucose, or both. There were no differences in thymocyte glucose or glutamine metabolism between normal and diabetic BB rats, in contrast to previous findings in peripheral lymphoid organs. Our results suggest that glucose is a more important fuel than glutamine for "resting" thymocytes, again in contrast to the cells of peripheral lymphoid organs in which glutamine is as important as glucose as a fuel. The enhanced energy metabolism found in the cells from peripheral lymphoid organs of diabetic BB rats, if due to T-lymphocytes, must occur after their migration out of the thymus.Key words: glutaminolysis, glycolysis, thymocytes, ATP, BB rats.

Epidemiologia zaburzeń neuropoznawczych u pacjentów w wieku podeszłym

2018 ◽  
Vol 21 (3) ◽  
Author(s):  
Wioletta Mędrzycka-Dąbrowska ◽  
Katarzyna Kwiecień-Jaguś ◽  
Renata Piotrkowska ◽  
Piotr Jarzynkowski
Keyword(s):  
The Elderly ◽  
Brain Dysfunction ◽  
Aging Brain ◽  
Psychomotor Slowing ◽  
Functional Changes ◽  
Slowing Down ◽  
Memory Functioning ◽  
Compensation Mechanisms ◽  
Key Issues ◽  
The Brain

The phenomenon of progressive impairment of cognitive functions is characteristic for the aging process. More than half of people over 50 complain about weakening of their previous intellectual performance, reduced mood, impaired memory, psychomotor slowing down, decreased ability to concentrate and divide attention, extend reaction time and reduce motor performance. The basis of mental changes in the elderly are changes in the brain. The changes arising in the aging brain are the result of pathological processes: metabolic and altered cerebral circulation. These changes, and mainly their extent, consequently cause brain dysfunction and are manifested mainly in the deterioration of mental functions. The brain is first and foremost the material basis of a mental life. With age, slow, cumulative and irreversible morphological and functional changes occur in the human brain. This process is slow, which is why it is accompanied by a number of compensation mechanisms. This phenomenon occurs regardless of gender. The aim of this article is to present the key issues related to memory functioning in the elderly, with particular emphasis on neurocognitive impairment after surgery.

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