DOCSLIB.ORG

The Perimenopausal Aging Transition in the Female Rat Brain: Decline in Bioenergetic Systems and Synaptic Plasticity

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Perimenopausal Aging Transition in the Female Rat Brain: Decline in Bioenergetic Systems and Synaptic Plasticity Neurobiology of Aging 36 (2015) 2282e2295 Contents lists available at ScienceDirect Neurobiology of Aging journal homepage: www.elsevier.com/locate/neuaging The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity Fei Yin a, Jia Yao a, Harsh Sancheti a, Tao Feng b, Roberto C. Melcangi c, Todd E. Morgan d, Caleb E. Finch d, Christian J. Pike d, Wendy J. Mack b, Enrique Cadenas a, Roberta D. Brinton a,e,* a Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA b Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA c Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy d Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA e Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA article info abstract Article history: The perimenopause is an aging transition unique to the female that leads to reproductive senescence Received 19 December 2014 which can be characterized by multiple neurological symptoms. To better understand potential under- Received in revised form 20 February 2015 lying mechanisms of neurological symptoms of perimenopause, the present study determined genomic, Accepted 25 March 2015 biochemical, brain metabolic, and electrophysiological transformations that occur during this transition Available online 1 April 2015 using a rat model recapitulating fundamental characteristics of the human perimenopause. Gene expression analyses indicated two distinct aging programs: chronological and endocrine. A critical period Keywords: emerged during the endocrine transition from regular to irregular cycling characterized by decline in Perimenopause fi fi fl e Female brain aging bioenergetic gene expression, con rmed by de cits in uorodeoxyglucose positron emission tomog- Glucose metabolism raphy (FDG-PET) brain metabolism, mitochondrial function, and long-term potentiation. Bioinformatic Mitochondria analysis predicted insulin/insulin-like growth factor 1 and adenosine monophosphate-activated protein Synaptic plasticity kinase/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK/PGC1a) signaling Hypometabolism pathways as upstream regulators. Onset of acyclicity was accompanied by a rise in genes required for Fatty acid metabolism fatty acid metabolism, inflammation, and mitochondrial function. Subsequent chronological aging Long-term potentiation resulted in decline of genes required for mitochondrial function and b-amyloid degradation. Emergence of glucose hypometabolism and impaired synaptic function in brain provide plausible mechanisms of neurological symptoms of perimenopause and may be predictive of later-life vulnerability to hypo- metabolic conditions such as Alzheimer’s. Ó 2015 Elsevier Inc. All rights reserved. 1. Introduction complete decrease in ovarian secretion of estrogen and progester- one hormones (Harlow et al., 2012). Similar to the human, rodent The perimenopause, unique to the female, is a midlife transition and nonhuman primates share common features of the perimen- state that precedes and leads to reproductive senescence (Brinton, opausal transition, including decline in follicles, irregular cycling, 2010; Butler and Santoro, 2011). Worldwide, there are currently irregular fertility, steroid hormone fluctuations, and insensitivity to >850 million women aged 40e60 years, 88% of whom will transi- estrogen (Brinton, 2012; Finch, 2014). tion through the perimenopause by age 55; all women who reach Although the clinical definition of perimenopause focuses on the age of 60 with reproductive organs intact will transition functional changes in the reproductive system, the symptoms of the through the perimenopause to the menopause (Brinton, 2010; perimenopause are largely neurological in nature. The breadth of Harlow et al., 2012). This final stage is associated with a near neurological symptoms coincident with the perimenopause is well documented in the clinical science literature (Genazzani et al., 2005; Greendale et al., 2010; Maki et al., 2008; Nelson, 2008). These neurological symptoms including increased temperature, * Corresponding author at: Department of Pharmacology and Pharmaceutical depression, insomnia, pain, and cognitive impairment during the Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, PSC-502, Los Angeles, CA 90089, USA. Tel.: 323 442 1436; fax: 323 442 1740. perimenopausal transition are indicative of disruption in multiple E-mail address: [email protected] (R.D. Brinton). systems, whereas their emergence during the same transition is 0197-4580/$ e see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.neurobiolaging.2015.03.013 F. Yin et al. / Neurobiology of Aging 36 (2015) 2282e2295 2283 indicative of a common or a set of common underlying mecha- and irregular 9e10 month groups (20 rats in total) was used for LTP nisms. Substantial evidence indicates that ovarian and neural hor- (Fig. 6). Rats that did not meet the endocrine criteria for each group mones including 17b-estradiol (E2) and progesterone (P4) regulate were excluded from analyses for this study. fundamental systems in brain at both the organizational and acti- vational levels including neurogenesis, cell survival, brain meta- 2.2. Brain tissue collection bolism, neuroinflammation, and synaptic activity (Brinton, 2008, 2009; Brinton et al., 2008; McEwen et al., 2012; Morrison et al., Rats were euthanized and the brains rapidly dissected on ice. 2006; Rettberg et al., 2014; Simpkins et al., 2010; Woolley, 2007; Cerebellum and brain stem were removed from each brain and two Yao et al., 2011). hemispheres were separated. The cortical hemisphere was fully The present perimenopause model builds on prior studies in peeled laterally and hippocampus was then separated. Both cortex middle-aged rats during their transition from regular to irregular and hippocampus were harvested and frozen in À80 C for subse- cycling (Adams et al., 2001; Downs and Wise, 2009; Finch et al., quent analyses. 1984; Gore et al., 2000; Kermath and Gore, 2012). The transition to irregular cycles was associated with cognitive impairments and 2.3. Quantitative analysis of steroid hormones by liquid altered sex steroids in hippocampus and cerebral cortex (Paris et al., chromatography-tandem mass spectrometry (LC-MS/MS) 2011), while we found altered expression of estrogen receptor a (ERa) in astrocytes of cerebral cortex with altered neurotrophic Levels of P4 and E2 extracted from cerebral cortex and serum were activity in vitro (Arimoto et al., 2013). To investigate potential measured as previously described (Caruso et al., 2013). 2,2,4,6,6- underlying mechanisms of neurological dysfunction during the 17a,21,21,21-D9-PROG (D9-PROG) was obtained from Medical Iso- perimenopause, we conducted neural analyses in endocrine- topes, (Pelham, NH, USA); 2,3,4e13C3-17b-estradiol (13C3-17b-E) was characterized rats spanning the transition from reproductively obtained from Sigma-Aldrich. Solid phase extraction (SPE) cartridges capable to reproductive senescent to aged. Using this model, we (Discovery DS-C18 500 mg) were from Supelco, Italy. Cerebral cortex investigated the differential impact of endocrine aging versus and serum were spiked with 13C3-17b-E (1 ng/sample) and D9-PROG chronological aging on hippocampal bioenergetic systems (glucose (0.2 ng/sample), as internal standards and homogenized in 2 mL of metabolism, inflammation, redox, lipid metabolism, and b-amyloid MeOH to acetic acid (99:1 vol/vol). After an overnight extraction at 4 processing) and synaptic function (long-term potentiation [LTP]). C, samples were centrifuged at 12,000 rpm for 5 minutes, and the Findings from this study revealed bioenergetic transitions specific pellet was extracted twice with 1 mL of MeOH to acetic acid (99:1 vol/ to endocrine aging during the perimenopause, that were coincident vol). The organic phases were combined and evaporated to dryness. with significant decline in synaptic plasticity. The organic residues were resuspended with 3 mL of MeOH to H2O (10:90 vol/vol) and passed through an SPE cartridge, previously acti- 2. Methods vated with MeOH (5 mL) and MeOH:H2O 1:9 vol/vol (5 mL), the ste- roids were eluted in MeOH. Quantitative analysis was performed on 2.1. Animals the basis of calibration curves daily prepared and analyzed. Positive atmospheric pressure chemical ionization experiments were per- Animal studies were performed following National Institutes of formed with a linear ion trapemass spectrometer (LTQ, Thermo- Health guidelines on use of laboratory animals; protocols were Electron Co, San Jose, CA, USA) using nitrogen as sheath, auxiliary, and approved by the Universityof Southern CaliforniaInstitutional Animal sweep gas. The mass spectrometer (MS) was employed in tandem Care and Use Committee. A total of 90 young or middle-aged female mode (MS/MS) using helium as collision gas. The Hypersil GOLD Sprague-Dawley rats were obtained from Harlan Laboratories. Regu- column (100 Â 3mm,3mm; ThermoElectron Co) wasmaintained at40 lar 6-month group was cycled from 5 months of age using rats that had C. Peaks of the LC-MS/MS were evaluated by means of the software given birth to at least 1 litter. Rats for all other groups were aged from Excalibur release 2.0 SR2. The steroids
Load more

Recommended publications
  • Bioenergetic Abnormalities in Schizophrenia
    Bioenergetic abnormalities in schizophrenia A dissertation submitted to the Graduate School of the University of Cincinnati in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate Program in Neuroscience of the College of Medicine by Courtney René Sullivan B.S. University of Pittsburgh, 2013 Dissertation Committee: Mark Baccei, Ph.D. (chair) Robert McCullumsmith, M.D., Ph.D. (advisor) Michael Lieberman, Ph.D. Temugin Berta, Ph.D. Robert McNamara, Ph.D. ABSTRACT Schizophrenia is a devastating illness that affects over 2 million people in the U.S. and displays a wide range of psychotic symptoms, as well as cognitive deficits and profound negative symptoms that are often treatment resistant. Cognition is intimately related to synaptic function, which relies on the ability of cells to obtain adequate amounts of energy. Studies have shown that disrupting bioenergetic pathways affects working memory and other cognitive behaviors. Thus, investigating bioenergetic function in schizophrenia could provide important insights into treatments or prevention of cognitive disorders. There is accumulating evidence of bioenergetic dysfunction in chronic schizophrenia, including deficits in energy storage and usage in the brain. However, it is unknown if glycolytic pathways are disrupted in this illness. This dissertation employs a novel reverse translational approach to explore glycolytic pathways in schizophrenia, effectively combining human postmortem studies with bioinformatic analyses to identify possible treatment strategies, which we then examine in an animal model. To begin, we characterized a major pathway supplying energy to neurons (the lactate shuttle) in the dorsolateral prefrontal cortex (DLPFC) in chronic schizophrenia. We found a significant decrease in the activity of two key glycolytic enzymes in schizophrenia (hexokinase, HXK and phosphofructokinase, PFK), suggesting a decrease in the capacity to generate bioenergetic intermediates through glycolysis in this illness.
    [Show full text]
  • Biochemical Fossils of the Ancient Transition from Geoenergetics to Bioenergetics in Prokaryotic One Carbon Compound Metabolism☆
    BBABIO-47248; No. of pages: 18; 4C: 4, 6, 7, 9 Biochimica et Biophysica Acta xxx (2014) xxx–xxx Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbabio Biochemical fossils of the ancient transition from geoenergetics to bioenergetics in prokaryotic one carbon compound metabolism☆ Filipa L. Sousa, William F. Martin ⁎ Institute for Molecular Evolution,University of Düsseldorf, 40225 Düsseldorf, Germany article info abstract Article history: The deep dichotomy of archaea and bacteria is evident in many basic traits including ribosomal protein compo- Received 26 October 2013 sition, membrane lipid synthesis, cell wall constituents, and flagellar composition. Here we explore that deep di- Received in revised form 31 January 2014 chotomy further by examining the distribution of genes for the synthesis of the central carriers of one carbon Accepted 3 February 2014 units, tetrahydrofolate (H F) and tetrahydromethanopterin (H MPT), in bacteria and archaea. The enzymes un- Available online xxxx 4 4 derlying those distinct biosynthetic routes are broadly unrelated across the bacterial–archaeal divide, indicating Keywords: that the corresponding pathways arose independently. That deep divergence in one carbon metabolism is mir- Pterins rored in the structurally unrelated enzymes and different organic cofactors that methanogens (archaea) and Hydrothermal vents acetogens (bacteria) use to perform methyl synthesis in their H4F- and H4MPT-dependent versions, respectively, Origin of life of the acetyl-CoA pathway. By contrast, acetyl synthesis in the acetyl-CoA pathway — from a methyl group, CO2 Methanogens and reduced ferredoxin — is simpler, uniform and conserved across acetogens and methanogens, and involves Acetogens only transition metals as catalysts.
    [Show full text]
  • Revolutionizing Neurodegenerative Disease Using Bioenergetic Nanotherapeutics to Improve Patients‘ Lives
    CLENE INC. ANNUAL REPORT 2020 REPORT ANNUAL REVOLUTIONIZING NEURODEGENERATIVE DISEASE USING BIOENERGETIC NANOTHERAPEUTICS TO IMPROVE PATIENTS‘ LIVES ANNUAL REPORT 2020 Breakthrough Needed for Patients Eective treatment of patients with neurodegenerative disorders requires a therapeutic breakthrough. The World Health Organization predicts diseases of neurodegeneration will become the second-most prevalent cause of death within the next 20 years1. Bioenergetic Opportunity Bioenergetic failure underlies the pathophysiology of many neurodegenerative diseases2. However, rescuing failing bioenergetic systems in these diseases has historically been extremely challenging3. Bioenergetic Nanotherapeutics Clene® is rapidly advancing a pipeline of bioenergetic nanotherapeutics, the first of those is CNM-Au8, designed to enhance naturally occurring cellular metabolism with the goal of reversing neurodegeneration. This new class of drugs called bioenergetic nanocatalysts has been created to accelerate neurorepair, improve neuroprotection, and enhance remyelination4. Innovative Platform The innovative platform is an electrochemistry approach to growing clean-surfaced, metallic nanocrystal therapeutics. The nanotherapeutic CNM-Au8 is designed to optimize cellular health and repair through energy enhancing bioenergetic catalysis. Using pure, clean-surfaced gold nanocrystals, we are able to amplify healthy, intracellular reactions necessary for cells to function and defend CLENE themselves from disease4. INNOVATE PROTECT REPAIR BIOENERGETIC NANOTHERAPEUTICS CNM-Au8 Clene Team Clene carefully engineered its lead drug Behind every innovative platform is a candidate, CNM-Au8, a bioenergetic team of inventive minds. Clene nanocatalyst which enhances critical enlisted a leadership team of intracellular bioenergetic reactions seasoned industry veterans united by necessary for repairing and reversing their appetite for innovation and neuronal damage. Orally administered, committed to advancing the CNM-Au8 has demonstrated safety in Phase company’s pipeline rapidly.
    [Show full text]
  • Estrogen: a Master Regulator of Bioenergetic Systems in the Brain and Body ⇑ Jamaica R
    Frontiers in Neuroendocrinology 35 (2014) 8–30 Contents lists available at ScienceDirect Frontiers in Neuroendocrinology journal homepage: www.elsevier.com/locate/yfrne Review Estrogen: A master regulator of bioenergetic systems in the brain and body ⇑ Jamaica R. Rettberg a, Jia Yao b, Roberta Diaz Brinton a,b,c, a Neuroscience Department, University of Southern California, Los Angeles, CA 90033, United States b Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, United States c Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States article info abstract Article history: Estrogen is a fundamental regulator of the metabolic system of the female brain and body. Within the Available online 29 August 2013 brain, estrogen regulates glucose transport, aerobic glycolysis, and mitochondrial function to generate ATP. In the body, estrogen protects against adiposity, insulin resistance, and type II diabetes, and regu- Keywords: lates energy intake and expenditure. During menopause, decline in circulating estrogen is coincident with Adipokine decline in brain bioenergetics and shift towards a metabolically compromised phenotype. Compensatory Adipose tissue bioenergetic adaptations, or lack thereof, to estrogen loss could determine risk of late-onset Alzheimer’s Aging disease. Estrogen coordinates brain and body metabolism, such that peripheral metabolic state can indi- Alzheimer’s disease cate bioenergetic status of the brain. By generating biomarker profiles that encompass peripheral meta- Biomarker Insulin bolic changes occurring with menopause, individual risk profiles for decreased brain bioenergetics and Menopause cognitive decline can be created. Biomarker profiles could identify women at risk while also serving as Metabolism indicators of efficacy of hormone therapy or other preventative interventions.
    [Show full text]
  • Do We Have a Thermotrophic Feature? James Weifu Lee
    www.nature.com/scientificreports OPEN Mitochondrial energetics with transmembrane electrostatically localized protons: do we have a thermotrophic feature? James Weifu Lee Transmembrane electrostatically localized protons (TELP) theory has been recently recognized as an important addition over the classic Mitchell’s chemiosmosis; thus, the proton motive force (pmf) is largely contributed from TELP near the membrane. As an extension to this theory, a novel phenomenon of mitochondrial thermotrophic function is now characterized by biophysical analyses of pmf in relation to the TELP concentrations at the liquid-membrane interface. This leads to the conclusion that the oxidative phosphorylation also utilizes environmental heat energy associated with the thermal kinetic energy (kBT) of TELP in mitochondria. The local pmf is now calculated to be in a range from 300 to 340 mV while the classic pmf (which underestimates the total pmf) is in a range from 60 to 210 mV in relation to a range of membrane potentials from 50 to 200 mV. Depending on TELP concentrations in mitochondria, this thermotrophic function raises pmf signifcantly by a factor of 2.6 to sixfold over the classic pmf. Therefore, mitochondria are capable of efectively utilizing the environmental heat energy with TELP for the synthesis of ATP, i.e., it can lock heat energy into the chemical form of energy for cellular functions. In the past, there was a common belief that the living organisms on Earth could only utilize light energy and/ or chemical energy, but not the environmental heat energy. Consequently, the life on Earth has been classifed as two types based on their sources of energy: phototrophs and chemotrophs.
    [Show full text]
  • Energy Conservation Via Electron Bifurcating Ferredoxin Reduction and Proton/Na+ Translocating Ferredoxin Oxidation☆
    Biochimica et Biophysica Acta 1827 (2013) 94–113 Contents lists available at SciVerse ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbabio Review Energy conservation via electron bifurcating ferredoxin reduction and proton/Na+ translocating ferredoxin oxidation☆ Wolfgang Buckel ⁎, Rudolf K. Thauer Max-Planck-Institut für terrestrische Mikrobiologie, Karl-von-Frisch-Str. 10, 35043 Marburg, and Fachbereich Biologie, Philipps-Universität, Marburg, Germany article info abstract Article history: The review describes four flavin-containing cytoplasmatic multienzyme complexes from anaerobic bacteria Received 9 May 2012 and archaea that catalyze the reduction of the low potential ferredoxin by electron donors with higher poten- Received in revised form 5 July 2012 tials, such as NAD(P)H or H2 at ≤100 kPa. These endergonic reactions are driven by concomitant oxidation of Accepted 7 July 2012 the same donor with higher potential acceptors such as crotonyl-CoA, NAD+ or heterodisulfide Available online 16 July 2012 (CoM-S-S-CoB). The process called flavin-based electron bifurcation (FBEB) can be regarded as a third mode of energy conservation in addition to substrate level phosphorylation (SLP) and electron transport Keywords: Flavin-based electron bifurcation (FBEB) phosphorylation (ETP). FBEB has been detected in the clostridial butyryl-CoA dehydrogenase/electron trans- Flavin semiquinone ferring flavoprotein complex (BcdA-EtfBC), the multisubunit [FeFe]hydrogenase from Thermotoga maritima Etf-Butyryl-CoA Dehydrogenase Complex (HydABC) and from acetogenic bacteria, the [NiFe]hydrogenase/heterodisulfide reductase (MvhADG–HdrABC) [FeFe] and [FeNi]hydrogenases from methanogenic archaea, and the transhydrogenase (NfnAB) from many Gram positive and Gram negative NADH:NADPH Transhydrogenase bacteria and from anaerobic archaea.
    [Show full text]
  • Why Chloroplasts and Mitochondria Retain Their Own Genomes
    PAPER Why chloroplasts and mitochondria retain their own COLLOQUIUM genomes and genetic systems: Colocation for redox regulation of gene expression John F. Allen1 Research Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom Edited by Patrick J. Keeling, University of British Columbia, Vancouver, BC, Canada, and accepted by the Editorial Board April 26, 2015 (received for review January 1, 2015) Chloroplasts and mitochondria are subcellular bioenergetic organ- control. Fig. 2B illustrates the two possible pathways of synthesis elles with their own genomes and genetic systems. DNA replica- of each of the three token proteins, A, B, and C. Synthesis may tion and transmission to daughter organelles produces cytoplasmic begin with transcription of genes in the endosymbiont or of gene inheritance of characters associated with primary events in photo- copies acquired by the host. CoRR proposes that gene location synthesis and respiration. The prokaryotic ancestors of chloroplasts by itself has no structural or functional consequence for the and mitochondria were endosymbionts whose genes became mature form of any protein whereas natural selection never- copied to the genomes of their cellular hosts. These copies gave theless operates to determine which of the two copies is retained. Selection favors continuity of redox regulation of gene A, and rise to nuclear chromosomal genes that encode cytosolic proteins ’ and precursor proteins that are synthesized in the cytosol for import this regulation is sufficient to render the host s unregulated copy into the organelle into which the endosymbiont evolved. What redundant. In contrast, there is a selective advantage to location of genes B and C in the genome of the host (5), and thus it is the accounts for the retention of genes for the complete synthesis endosymbiont copies of B and C that become redundant and are within chloroplasts and mitochondria of a tiny minority of their lost.
    [Show full text]
  • Bioenergetics, the Origins of Complexity, and the Ascent of Man
    Bioenergetics, the origins of complexity, and the ascent of man Douglas C. Wallace1 Organized Research Unit for Molecular and Mitochondrial Medicine and Genetics and Departments of Ecology and Evolutionary Biology, Biological Chemistry, and Pediatrics, University of California, Irvine, CA 92697-3940 Complex structures are generated and maintained through energy The flow of energy through biological structures permits them to flux. Structures embody information, and biological information is reproduce, thus duplicating their DNA. In the process of DNA stored in nucleic acids. The progressive increase in biological com- copying, errors occur. The duplicated mutant DNA changes the plexity over geologic time is thus the consequence of the information- physiology and structure of the progeny. These progeny must com- fl generating power of energy ow plus the information-accumulating pete for the available energy resources within the environment. capacity of DNA, winnowed by natural selection. Consequently, the Those that are more effective at acquiring and/or expending the most important component of the biological environment is energy fl flow: the availability of calories and their use for growth, survival, and available energy will sustain their energy ux and thus survive and reproduction. Animals can exploit and adapt to available energy reproduce. This competition for limited energy resources is the basis resources at three levels. They can evolve different anatomical forms of natural selection, which edits the duplicated information based
    [Show full text]
  • Fatigability and Cardiorespiratory Impairments in Parkinson's Disease
    Journal of Functional Morphology and Kinesiology Review Fatigability and Cardiorespiratory Impairments in Parkinson’s Disease: Potential Non-Motor Barriers to Activity Performance Andrew E. Pechstein 1 , Jared M. Gollie 1,2,3,* and Andrew A. Guccione 1 1 Department of Rehabilitation Science, George Mason University, Fairfax, VA 22030, USA; [email protected] (A.E.P.); [email protected] (A.A.G.) 2 Research Services, Veterans Affairs Medical Center, Washington, DC 20422, USA 3 Department of Health, Human Function, and Rehabilitation Sciences, The George Washington University, Washington, DC 20006, USA * Correspondence: [email protected] Received: 28 September 2020; Accepted: 29 October 2020; Published: 31 October 2020 Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative condition after Alzheimer’s disease, affecting an estimated 160 per 100,000 people 65 years of age or older. Fatigue is a debilitating non-motor symptom frequently reported in PD, often manifesting prior to disease diagnosis, persisting over time, and negatively affecting quality of life. Fatigability, on the other hand, is distinct from fatigue and describes the magnitude or rate of change over time in the performance of activity (i.e., performance fatigability) and sensations regulating the integrity of the performer (i.e., perceived fatigability). While fatigability has been relatively understudied in PD as compared to fatigue, it has been hypothesized that the presence of elevated levels of fatigability in PD results from the interactions of homeostatic, psychological, and central factors. Evidence from exercise studies supports the premise that greater disturbances in metabolic homeostasis may underly elevated levels of fatigability in people with PD when engaging in physical activity.
    [Show full text]
  • Investigation of the Relationships That Exist Between Athletic Training, Hormones and Sleep in Young Healthy Male Athletes
    Copyright is owned by the Author of the thesis. Permission is given for a copy to be downloaded by an individual for the purpose of research and private study only. The thesis may not be reproduced elsewhere without the permission of the Author. Master of Science Thesis Investigation of the Relationships that Exist between Athletic Training, Hormones and Sleep in Young Healthy Male Athletes Lara Blackmore 2004 Abstract Background. Many people engage in exercise for recreation, to promote personal health and as a profession. Accordingly there is wide ranging interest in the factors that affect a person's performance during exercise and in how that performance can both be assessed and enhanced. The physiological basis of exercise performance and its enhancement have been investigated for many years. Such investigations in people are impeded by the understandable reluctance of participants to provide significant numbers of blood samples by venepuncture. The recent development of an ultrasound method for non­ invasive sampling of extracellular fluid, called transdermal electrosonophoresis (ESP), offers tremendous opportunities for benign monitoring of physiological responses involving changes in blood/extracellular fluid composition associated with exercise and indeed in clinical settings. Sleep quality/quantity is considered to have significant impact on training effectiveness and performance, with poor sleep correlated with poor athletic outcome. The link here is considered to involve growth hormone, as poor sleep quality/quantity diminishes growth hormone concentrations and reduced growth hormone concentrations impede training induced muscle development. Training effectiveness and recovery have been monitored in past research through measurement of blood hormone profiles, in particular the testosterone: cortisol ratio.
    [Show full text]
  • Driving Natural Systems: Chemical Energy Production and Use
    Driving natural systems: Chemical energy production and use Chemical energy and metabolism ATP usage and production Driving natural systems: Chemical Mitochondria and bioenergetic energy production and use control Modelling systems of chemical reactions Driving natural Metabolism systems: Chemical energy production and use I Metabolism: the sum of the physical and chemical processes Chemical energy in an organism by which its and metabolism material substance is produced, maintained, and destroyed ATP usage and production [anabolism], and by which energy is made available Mitochondria and bioenergetic [catabolism] control I Metabolism allows organisms to Modelling systems control biomass and energy of chemical reactions I A set of chemical transformations, often enzyme-catalysed I A complicated network: simplified through tools like flux balance analysis I Metabolism provides the energy for inference and control I Metabolism is itself controlled and regulated: metabolic control analysis, active regulation Driving natural Free energy systems: Chemical energy production I Energy that can be harnessed to perform work and use I At constant temperature and pressure (which we shall assume), the appropriate expression is the Gibbs free energy G(p; T ) Chemical energy and metabolism G(p; T ) = U + pV − TS ATP usage and production I Internal energy U, pressure p, volume V , temperature T , entropy S Mitochondria and bioenergetic I Change in free energy, where αj ; Xj are a feature and associated control potential that influence our system (e.g. N;
    [Show full text]
  • Mitochondria, Neurosteroids and Biological Rhythms: Implications in Health and Disease States
    Mitochondria, neurosteroids and biological rhythms : implications in health and disease states Amandine Grimm To cite this version: Amandine Grimm. Mitochondria, neurosteroids and biological rhythms : implications in health and disease states. Neurobiology. Université de Strasbourg, 2015. English. NNT : 2015STRAJ002. tel-01280544 HAL Id: tel-01280544 https://tel.archives-ouvertes.fr/tel-01280544 Submitted on 29 Feb 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSIT DE STRASBOURG Ecole Doctorale des Sciences de la Vie et de la Sant (ED 414) INSERM UMR_S U1119 M Biopathologies de la My line, Neuroprotection et Strat gies Th rapeutiques THSE En cotutelle avec lRUniversit de Ble, Suisse pr sent e par : Amandine GRIMM soutenue le 14 janvier 2015 pour obtenir le grade de : Docteur de lRUniversit de Strasbourg Sp cialit : Neurosciences Mitochondria, neurosteroids and biological rhythms: implications in health and disease states. THSE dirig e par : M. MENSAH-NYAGAN Ayiko , Guy Professeur, Universit de Strasbourg, France Mme ECKERT Anne Professeur,
    [Show full text]