Mitochondria and neuronal activity

2007 ◽  
Vol 292 (2) ◽  
pp. C641-C657 ◽  
Author(s):  
Oliver Kann ◽  
Richard Kovács
Keyword(s):  
Energy Metabolism ◽  
Neuronal Activity ◽  
Mitochondrial Function ◽  
Imaging Techniques ◽  
Neurological Diseases ◽  
Experimental Models ◽  
Metabolic Dysfunction ◽  
Membrane Excitability ◽  
Spatiotemporal Resolution ◽  
Atp Production

Mitochondria are central for various cellular processes that include ATP production, intracellular Ca2+ signaling, and generation of reactive oxygen species. Neurons critically depend on mitochondrial function to establish membrane excitability and to execute the complex processes of neurotransmission and plasticity. While much information about mitochondrial properties is available from studies on isolated mitochondria and dissociated cell cultures, less is known about mitochondrial function in intact neurons in brain tissue. However, a detailed description of the interactions between mitochondrial function, energy metabolism, and neuronal activity is crucial for the understanding of the complex physiological behavior of neurons, as well as the pathophysiology of various neurological diseases. The combination of new fluorescence imaging techniques, electrophysiology, and brain slice preparations provides a powerful tool to study mitochondrial function during neuronal activity, with high spatiotemporal resolution. This review summarizes recent findings on mitochondrial Ca2+ transport, mitochondrial membrane potential (ΔΨm), and energy metabolism during neuronal activity. We will first discuss interactions of these parameters for experimental stimulation conditions that can be related to the physiological range. We will then describe how mitochondrial and metabolic dysfunction develops during pathological neuronal activity, focusing on temporal lobe epilepsy and its experimental models. The aim is to illustrate that 1) the structure of the mitochondrial compartment is highly dynamic in neurons, 2) there is a fine-tuned coupling between neuronal activity and mitochondrial function, and 3) mitochondria are of central importance for the complex behavior of neurons.

scholarly journals Mitochondrial Dysfunction in Alzheimer’s Disease: A Biomarker of the Future?

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 63
Author(s):  
Simon M. Bell ◽  
Katy Barnes ◽  
Matteo De Marco ◽  
Pamela J. Shaw ◽  
Laura Ferraiuolo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Function ◽  
Imaging Techniques ◽  
The Body ◽  
Atp Production ◽  
Disease Modifying Therapies ◽  
Mitochondrial Functions ◽  
Species Production ◽  
The Brain

Alzheimer’s disease (AD) is the most common cause of dementia worldwide and is characterised pathologically by the accumulation of amyloid beta and tau protein aggregates. Currently, there are no approved disease modifying therapies for clearance of either of these proteins from the brain of people with AD. As well as abnormalities in protein aggregation, other pathological changes are seen in this condition. The function of mitochondria in both the nervous system and rest of the body is altered early in this disease, and both amyloid and tau have detrimental effects on mitochondrial function. In this review article, we describe how the function and structure of mitochondria change in AD. This review summarises current imaging techniques that use surrogate markers of mitochondrial function in both research and clinical practice, but also how mitochondrial functions such as ATP production, calcium homeostasis, mitophagy and reactive oxygen species production are affected in AD mitochondria. The evidence reviewed suggests that the measurement of mitochondrial function may be developed into a future biomarker for early AD. Further work with larger cohorts of patients is needed before mitochondrial functional biomarkers are ready for clinical use.

scholarly journals Quantitative Assessment of Occipital Metabolic and Energetic Changes in Parkinson’s Patients, Using In Vivo 31P MRS-Based Metabolic Imaging at 7T

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 145
Author(s):  
Xiao-Hong Zhu ◽  
Byeong-Yeul Lee ◽  
Paul Tuite ◽  
Lisa Coles ◽  
Abhishek G. Sathe ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Neurodegenerative Diseases ◽  
Intracellular Ph ◽  
Imaging Techniques ◽  
Neurological Deficits ◽  
Response To Treatment ◽  
Metabolic Imaging ◽  
Atp Production ◽  
31P Mrs

Abnormal energy metabolism associated with mitochondrial dysfunction is thought to be a major contributor to the progression of neurodegenerative diseases such as Parkinson’s disease (PD). Recent advancements in the field of magnetic resonance (MR) based metabolic imaging provide state-of-the-art technologies for non-invasively probing cerebral energy metabolism under various brain conditions. In this proof-of-principle clinical study, we employed quantitative 31P MR spectroscopy (MRS) imaging techniques to determine a constellation of metabolic and bioenergetic parameters, including cerebral adenosine triphosphate (ATP) and other phosphorous metabolite concentrations, intracellular pH and nicotinamide adenine dinucleotide (NAD) redox ratio, and ATP production rates in the occipital lobe of cognitive-normal PD patients, and then we compared them with age-sex matched healthy controls. Small but statistically significant differences in intracellular pH, NAD and ATP contents and ATPase enzyme activity between the two groups were detected, suggesting that subtle defects in energy metabolism and mitochondrial function are quantifiable before regional neurological deficits or pathogenesis begin to occur in these patients. Pilot data aiming to evaluate the bioenergetic effect of mitochondrial-protective bile acid, ursodeoxycholic acid (UDCA) were also obtained. These results collectively demonstrated that in vivo 31P MRS-based neuroimaging can non-invasively and quantitatively assess key metabolic-energetic metrics in the human brain. This provides an exciting opportunity to better understand neurodegenerative diseases, their progression and response to treatment.

Schisandrin Restores the Amyloid β-Induced Impairments on Mitochondrial Function, Energy Metabolism, Biogenesis, and Dynamics in Rat Primary Hippocampal Neurons

Pharmacology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Zhongyuan Piao ◽  
Lin Song ◽  
Lifen Yao ◽  
Limei Zhang ◽  
Yichan Lu
Keyword(s):  
Energy Metabolism ◽  
Cytochrome C ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Hippocampal Neurons ◽  
Citrate Synthase ◽  
Mitochondrial Permeability Transition ◽  
Amyloid Β ◽  
Mitochondrial Functions ◽  
Primary Hippocampal Neurons

Introduction: Schisandrin which is derived from Schisandra chinensis has shown multiple pharmacological effects on various diseases including Alzheimer’s disease (AD). It is demonstrated that mitochondrial dysfunction plays an essential role in the pathogenesis of neurodegenerative disorders. Objective: Our study aims to investigate the effects of schisandrin on mitochondrial functions and metabolisms in primary hippocampal neurons. Methods: In our study, rat primary hippocampal neurons were isolated and treated with indicated dose of amyloid β1–42 (Aβ1–42) oligomer to establish a cell model of AD in vitro. Schisandrin (2 μg/mL) was further subjected to test its effects on mitochondrial function, energy metabolism, mitochondrial biogenesis, and dynamics in the Aβ1–42 oligomer-treated neurons. Results and Conclusions: Our findings indicated that schisandrin significantly alleviated the Aβ1–42 oligomer-induced loss of mitochondrial membrane potential and impaired cytochrome c oxidase activity. Additionally, the opening of mitochondrial permeability transition pore and release of cytochrome c were highly restricted with schisandrin treatment. Alterations in cell viability, ATP production, citrate synthase activity, and the expressions of glycolysis-related enzymes demonstrated the relief of defective energy metabolism in Aβ-treated neurons after the treatment of schisandrin. For mitochondrial biogenesis, elevated expression of peroxisome proliferator-activated receptor γ coactivator along with promoted mitochondrial mass was found in schisandrin-treated cells. The imbalance in the cycle of fusion and fission was also remarkably restored by schisandrin. In summary, this study provides novel mechanisms for the protective effect of schisandrin on mitochondria-related functions.

Evolutionary Consequences of Tradeoffs between Yield and Rate of ATP Production

2002 ◽  
Vol 216 (1) ◽  
Author(s):  
Thomas Pfeiffer ◽  
Sebastian Bonhoeffer
Keyword(s):  
Game Theory ◽  
Population Dynamics ◽  
Energy Metabolism ◽  
Adenosine Triphosphate ◽  
Organic Material ◽  
High Yield ◽  
Atp Production ◽  
Cellular Processes ◽  
Quantitative Properties ◽  
Evolutionary Consequences

Adenosine triphosphate (ATP) is a key compound in the energy metabolism of cells and is required to drive vital biochemical reactions. In heterotrophic organisms ATP production is coupled to the degradation of energy-rich organic material taken up from the environment. In the transfer of the environmental energy to cellular processes heterotrophs face a tradeoff, since the conversion of the environmental energy into ATP cannot be both maximally fast and efficient. Here we show how tradeoffs between rate and yield of ATP production arise firstly from thermodynamical principles, and secondly for the ATP production by respiration and fermentation. Using methods derived from game theory and population dynamics we investigate the evolutionary consequences for both tradeoffs. We show that spatially structured environments enable the evolution of efficient pathways with high yield. The strategies of ATP production realized in a population, however, depend on the quantitative properties of the tradeoffs.

scholarly journals Relationships between dietary macronutrients and adult neurogenesis in the regulation of energy metabolism – CORRIGENDUM

2013 ◽  
Vol 111 (4) ◽  
pp. 755-755
Author(s):  
Marianne A. Yon ◽  
Suzanna L. Mauger ◽  
Lucy C. Pickavance
Keyword(s):  
Body Weight ◽  
Energy Metabolism ◽  
Adult Neurogenesis ◽  
Brain Regions ◽  
The Body ◽  
Adult Brain ◽  
Metabolic Dysfunction ◽  
Neurogenic Niche ◽  
Normal Limits ◽  
Simple Carbohydrates

Of the environmental factors which have an impact on body weight, nutrients are most influential. Within normal limits, hypothalamic and related neuronal populations correct perturbations in energy metabolism, to return the body to its nutritional set-point, either through direct response to nutrients or indirectly via peripheral appetite signals. Excessive intake of certain macronutrients, such as simple carbohydrates and SFA, can lead to obesity and attendant metabolic dysfunction, also reflected in alterations in structural plasticity, and, intriguingly, neurogenesis, in some of these brain regions. Neurogenesis, previously thought to occur only in the embryo, is now known to take place in the adult brain, dependent on numerous stimulating and inhibiting factors, including dietary components. Because of classic associations between neurogenesis and the hippocampus, in learning and cognition, this brain region has also been the focus of attention in the study of links between diet and neurogenesis. Recently, however, a more complete picture of this relationship has been building: not only has the hypothalamus been shown to satisfy the criteria for a neurogenic niche, but appetite-related mediators, including circulating hormones, such as leptin and ghrelin, pro-inflammatory cytokines and the endocannabinoid intracellular messengers, are also being examined for their potential role in mediating neurogenic responses to macronutrients. The present review draws together these observations and investigates whether n-3 PUFA may exert their attenuating effects on body weight through the stimulation of adult neurogenesis. Exploration of the effects of nutraceuticals on neurogenic brain regions may encourage the development of new rational therapies in the fight against obesity.

ATP depletion and mitochondrial functional loss during ischemia in slow and fast heart-rate hearts

1990 ◽  
Vol 259 (6) ◽  
pp. H1759-H1766 ◽  
Author(s):  
W. Rouslin ◽  
C. W. Broge ◽  
I. L. Grupp
Keyword(s):  
Mitochondrial Function ◽  
Atp Depletion ◽  
Mitochondrial Atpase ◽  
Small Contribution ◽  
Bicarbonate Buffer ◽  
Tissue Ph ◽  
Atp Production ◽  
Dog Heart ◽  
Rat Hearts

In the present study, isolated dog and rat hearts were perfused in the Langendorff mode with Krebs bicarbonate buffer in the absence and presence of 10(-5) M oligomycin. The perfusion protocols employed allowed tissue pH to drop during subsequent ischemic incubations essentially as it would in blood-perfused hearts. Tissue pH, ATP, lactate, and mitochondrial respiratory function were measured during the course of subsequent zero-flow ischemic incubations. The adenosinetriphosphatase (ATPase) activities attributable to both mitochondrial and nonmitochondrial ATPases in sonicated heart homogenates and the actomyosin ATPase in isolated cardiac myofibrils were measured in both species. Consistent with earlier results with a different model in which tissue pH was buffered during the ischemic incubations [W. Rouslin, J. L. Erickson, and R. J. Solaro. Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H503-H508, 1986], the inhibition of the mitochondrial ATPase in situ by oligomycin markedly slowed both tissue ATP depletion and the loss of mitochondrial function during ischemia in the dog. However, oligomycin had only a very small and transient effect on ATP depletion and mitochondrial function in the rat. This was apparently so because of the fivefold higher rate of glycolytic ATP production as well as the nearly threefold higher total nonmitochondrial ATPase activity of ischemic rat compared with ischemic dog heart. These results suggest that although the inhibition of the mitochondrial ATPase makes a major contribution to ATP conservation in ischemic dog heart, it makes only a very small contribution in rat.

Enhanced Ih Depresses Rat Entopeduncular Nucleus Neuronal Activity From High-Frequency Stimulation or Raised Ke+

2008 ◽  
Vol 99 (5) ◽  
pp. 2203-2219 ◽  
Author(s):  
D. S. Shin ◽  
P. L. Carlen
Keyword(s):  
Neuronal Activity ◽  
High Frequency ◽  
Neurological Diseases ◽  
Input Resistance ◽  
High Frequency Stimulation ◽  
Channel Activity ◽  
Entopeduncular Nucleus ◽  
Inhibitory Effects ◽  
Frequency Stimulation ◽  
Spontaneous Action

High-frequency stimulation (HFS) is used to treat a variety of neurological diseases, yet its underlying therapeutic action is not fully elucidated. Previously, we reported that HFS-induced elevation in [K+]e or bath perfusion of raised Ke+ depressed rat entopeduncular nucleus (EP) neuronal activity via an enhancement of an ionic conductance leading to marked depolarization. Herein, we show that the hyperpolarization-activated ( Ih) channel mediates the HFS- or K+-induced depression of EP neuronal activity. The perfusion of an Ih channel inhibitor, 50 μM ZD7288 or 2 mM CsCl, increased input resistance by 23.5 ± 7% (ZD7288) or 35 ± 10% (CsCl), hyperpolarized cells by 3.4 ± 1.7 mV (ZD7288) or 2.3 ± 0.9 mV (CsCl), and decreased spontaneous action potential (AP) frequency by 51.5 ± 12.5% (ZD7288) or 80 ± 13.5% (CsCl). The Ih sag was absent with either treatment, suggesting a block of Ih channel activity. Inhibition of the Ih channel prior to HFS or 6 mM K+ perfusion not only prevented the previously observed decrease in AP frequency, but increased neuronal activity. Under voltage-clamp conditions, Ih currents were enhanced in the presence of 6 mM K+. Calcium is also involved in the depression of EP neuronal activity, since its removal during raised Ke+ application prevented this attenuation and blocked the Ih sag. We conclude that the enhancement of Ih channel activity initiates the HFS- and K+-induced depression of EP neuronal activity. This mechanism could underlie the inhibitory effects of HFS used in deep brain stimulation in output basal ganglia nuclei.

scholarly journals Phytochemicals from the Cocoa Shell Modulate Mitochondrial Function, Lipid and Glucose Metabolism in Hepatocytes via Activation of FGF21/ERK, AKT, and mTOR Pathways

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 136
Author(s):  
Miguel Rebollo-Hernanz ◽  
Yolanda Aguilera ◽  
Maria A. Martin-Cabrejas ◽  
Elvira Gonzalez de Gonzalez de Mejia
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Cell Model ◽  
Fibroblast Growth Factor 21 ◽  
Alcoholic Fatty Liver ◽  
Atp Production ◽  
Cocoa Shell

The cocoa shell is a by-product that may be revalorized as a source of bioactive compounds to prevent chronic cardiometabolic diseases. This study aimed to investigate the phytochemicals from the cocoa shell as targeted compounds for activating fibroblast growth factor 21 (FGF21) signaling and regulating non-alcoholic fatty liver disease (NAFLD)-related biomarkers linked to oxidative stress, mitochondrial function, and metabolism in hepatocytes. HepG2 cells treated with palmitic acid (PA, 500 µmol L−1) were used in an NAFLD cell model. Phytochemicals from the cocoa shell (50 µmol L−1) and an aqueous extract (CAE, 100 µg mL−1) enhanced ERK1/2 phosphorylation (1.7- to 3.3-fold) and FGF21 release (1.4- to 3.4-fold) via PPARα activation. Oxidative stress markers were reduced though Nrf-2 regulation. Mitochondrial function (mitochondrial respiration and ATP production) was protected by the PGC-1α pathway modulation. Cocoa shell phytochemicals reduced lipid accumulation (53–115%) and fatty acid synthase activity (59–93%) and prompted CPT-1 activity. Glucose uptake and glucokinase activity were enhanced, whereas glucose production and phosphoenolpyruvate carboxykinase activity were diminished. The increase in the phosphorylation of the insulin receptor, AKT, AMPKα, mTOR, and ERK1/2 conduced to the regulation of hepatic mitochondrial function and energy metabolism. For the first time, the cocoa shell phytochemicals are proved to modulate FGF21 signaling. Results demonstrate the in vitro preventive effect of the phytochemicals from the cocoa shell on NAFLD.

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