Applications in Neurodegeneration

App Notes & Tech Briefs

• Bioenergetic Analysis of Primary Neuronal Deficiencies

  Sensitive assay to measure mitochondrial dysfunction characteristic of Parkinson's, Huntington's and other neurodegenerative diseases

  Mitochondria play central roles in meeting the demands of neuronal synapses for energy (ATP). Mitochondrial dysfunction results in impaired neuroplasticity, neuronal degeneration and cell death, and is now recognized as a key element in neurodegenerative diseases...

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• Assessing mitochondrial dysfunction in primary cardiomyocytes

  Mitochondrial reserve capacity is a sensitive measure of cellular stress

  This Application Note describes a method for profiling mitochondrial function in cells responding to stress. The mitochondrial profile generated in this way provides four parameters of mitochondrial function that can be measured in one experiment...

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• Screening for Mitochondrial Biogenesis and Toxicity

  A sensitive and robust cell-based screening assay.

  Mitochondrial damage compromises ATP production and consequentially cellular viability. Given the central role that mitochondria play in regulating cellular function, drugs that undermine mitochondrial function frequently elicit toxic effects...

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• Analyzing microgram quantities of isolated mitochondria in the XF24 Analyzer

  Enhanced appreciation of the role of altered mitochondrial function in tumorigenesis, aging, neurodegenerative, metabolic, and cardiovascular diseases has stimulated the development of a variety of new approaches for assessing mitochondrial function and dysfunction. As the field moves towards the discovery of mitochondrial-related, molecular mechanisms that underlie disease, and drugs to prevent or reverse disease development, the demand for higher throughput and more sensitive assay methods increases...

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Publications

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• Bioenergetic analysis of isolated cerebrocortical nerve terminals on a microgram scale: spare respiratory capacity and stochastic mitochondrial failure

  Choi S W, Gerencser A A and Nicholls D G

  J Neurochem; 2009 May 1. 109 (4):1179-1191.

• Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease

  Yao J, Irwin R W, Zhao L, Nilsen J, Hamilton R T and Brinton R D

  Proc Natl Acad Sci U S A; 2009 Aug 25. 106 (34):14670-14675.

• Mitochondrial Medicine and the Neurodegenerative Mitochondriopathies

  Swerdlow R H

  Pharmaceuticals; 2009 Dec 3. 2 (3):150-167.

• Nutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis

  Gohil V M, Sheth S A, Nilsson R, Wojtovich A P, Lee J H, Perocchi F, Chen W, Clish C B, Ayata C, Brookes P S and Mootha V K

  Nat Biotechnol; 2010 Mar 1. 28 (3):249-255.

• Loss of thymidine kinase 2 alters neuronal bioenergetics and leads to neurodegeneration

  Bartesaghi S, Betts-Henderson J, Cain K, Dinsdale D, Zhou X, Karlsson A, Salomoni P and Nicotera P

  Hum Mol Genet; 2010 May 1. 19 (9):1669-1677.

• Medroxyprogesterone Acetate Antagonizes Estrogen Up-Regulation of Brain Mitochondrial Function

  Irwin R W, Yao J, Ahmed S S, Hamilton R T, Cadenas E and Brinton R D

  Endocrinology; 2010 Dec 15. 152 (2):556-567.

• KB-R7943, an inhibitor of the reverse Na+ /Ca2+ exchanger, blocks N-methyl-D-aspartate receptor and inhibits mitochondrial complex I

  Brustovetsky T, Brittain M K, Sheets P L, Cummins T R, Pinelis V and Brustovetsky N

  Br J Pharmacol; 2011 Jan 1. 162 (1):255-270.

• Mitochondrial bioenergetics is defective in presymptomatic Tg2576 AD Mice

  Varghese M, Zhao W, Wang J, Cheng A, Qian X, Chaudhry A, Ho L and Pasinetti G

  Translational Neuroscience; 2011 Jan 5. 2 (1)

• Inducible dopaminergic glutathione depletion in an α-synuclein transgenic mouse model results in age-related olfactory dysfunction

  Kim Y H, Lussier S, Rane A, Choi S W and Andersen J K

  Neuroscience; 2011 Jan 13. 172 (1):379-386.

• Meclizine is neuroprotective in models of Huntington's disease

  Gohil V M, Offner N, Walker J A, Sheth S A, Fossale E, Gusella J F, Macdonald M E, Neri C and Mootha V K

  Hum Mol Genet; 2011 Jan 15. 20 (2):294-300.

• Apolipoprotein e4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease

  Chen H K, Ji Z S, Dodson S E, Miranda R D, Rosenblum C I, Reynolds I J, Freedman S B, Weisgraber K H, Huang Y and Mahley R W

  J Biol Chem; 2011 Feb 18. 286 (7):5215-5221.

• Mutations in TTC19 cause mitochondrial complex III deficiency and neurological impairment in humans and flies

  Ghezzi D, Arzuffi P, Zordan M, Da Re C, Lamperti C, Benna C, D'Adamo P, Diodato D, Costa R, Mariotti C, Uziel G, Smiderle C and Zeviani M

  Nat Genet; 2011 Mar 1. 43 (3):259-263.

• Glutamate Transport Decreases Mitochondrial pH and Modulates Oxidative Metabolism in Astrocytes

  Azarias G, Perreten H, Lengacher S, Poburko D, Demaurex N, Magistretti P J and Chatton J Y

  J Neurosci; 2011 Mar 9. 31 (10):3550-3559.

• Analysis of regional brain mitochondrial bioenergetics and susceptibility to mitochondrial inhibition utilizing a microplate based system

  Sauerbeck A, Pandya J, Singh I, Bittman K, Readnower R, Bing G and Sullivan P

  Journal of Neuroscience Methods; 2011 Mar 15. 198 (1):36-43.

• Estrogen protection against mitochondrial toxin-induced cell death in hippocampal neurons: Antagonism by progesterone

  Yao J, Chen S, Cadenas E and Brinton R D

  Brain Res; 2011 Mar 16. 1379 (1):40584.

• Intrinsic bioenergetic properties and stress sensitivity of dopaminergic synaptosomes

  Choi S W, Gerencser A A, Lee D W, Rajagopalan S, Nicholls D G, Andersen J K and Brand M D

  J Neurosci; 2011 Mar 23. 31 (12):4524-4534.

• Impaired spare respiratory capacity in cortical synaptosomes from Sod2 null mice

  Flynn J M, Choi S W, Day N U, Gerencser A A, Hubbard A and Melov S

  Free Radic Biol Med; 2011 Apr 1. 50 (7):866-873.

• Ovarian hormone loss induces bioenergetic deficits and mitochondrial beta-amyloid

  Yao J, Irwin R, Chen S, Hamilton R, Cadenas E and Brinton R D

  Neurobiol Aging. 2011 Apr 22; [Epub ahead of print].

• Alternative mitochondrial electron transfer as a novel strategy for neuroprotection

  Wen Y, Li W, Poteet E C, Xie L, Tan C, Yan L J, Ju X, Liu R, Qian H, Marvin M A, Goldberg M S, She H, Mao Z, Simpkins J W and Yang S H

  J Biol Chem; 2011 May 6. 286 (18):16504-16515.

• To eat or not to eat: neuronal metabolism, mitophagy, and Parkinson's disease

  Gusdon A M and Chu C T

  Antioxid Redox Signal; 2011 May 15. 14 (10):1979-1987.

• High-mobility group box 1 is essential for mitochondrial quality control

  Tang D, Kang R, Livesey K M, Kroemer G, Billiar T R, Van Houten B, Zeh H J, 3rd and Lotze M T

  Cell Metab; 2011 Jun 8. 13 (6):701-711.

• Mitochondrial aconitase knockdown attenuates paraquat-induced dopaminergic cell death via decreased cellular metabolism and release of iron and H(2) O(2)

  Cantu D, Fulton R E, Drechsel D A and Patel M

  J Neurochem; 2011 Jul 1. 118 (1):79-92.

• Mutation in the mitochondrial tRNAVal causes mitochondrial encephalopathy, lactic acidosis and stroke-like episodes

  Glatz C, D'Aco K, Smith S and Sondheimer N

  Mitochondrion; 2011 Jul 1. 11 (4):615-619.

• 2-deoxy-d-glucose treatment induces ketogenesis, sustains mitochondrial function, and reduces pathology in female mouse model of Alzheimer's disease

  Yao J, Chen S, Mao Z, Cadenas E and Brinton R D

  PLoS One. 2011 Jul 1; [Epub ahead of print].

• DHA protects against zinc mediated alterations in neuronal cellular bioenergetics

  McGee S L, Sadli N, Morrison S, Swinton C and Suphioglu C

  Cell Physiol Biochem; 2011 Aug 26. 28 (1):157-162.

• DJ-1 knock-down impairs astrocyte mitochondrial function

  Larsen N J, Ambrosi G, Mullett S J, Berman S B and Hinkle D A

  Neuroscience; 2011 Nov 24. (196):251-64.

• Mitochondrially localized PKA reverses mitochondrial pathology and dysfunction in a cellular model of Parkinson's disease

  Dagda R K, Gusdon A M, Pien I, Strack S, Green S, Li C, Van Houten B, Cherra S J, 3rd and Chu C T

  Cell Death Differ; 2011 Dec 1. 18 (12):1914-23.

• Differentiation of SH-SY5Y cells to a neuronal phenotype changes cellular bioenergetics and the response to oxidative stress

  Schneider L, Giordano S, Zelickson B R, Johnson M, Benavides G, Ouyang X, Fineberg N, Darley-Usmar V M and Zhang J

  Free Radical Biology and Medicine; 2011 Dec 1. 51 (11):2007-17.

• Adaptation of microplate-based respirometry for hippocampal slices and analysis of respiratory capacity

  Schuh R A, Clerc P, Hwang H, Mehrabian Z, Bittman K, Chen H and Polster B M

  J Neurosci Res; 2011 Dec 1. 89 (12):1979-1988.

• ATP13A2 regulates mitochondrial bioenergetics through macroautophagy

  Gusdon A M, Zhu J, Van Houten B and Chu C T

  Neurobiol Dis. 2011 Dec 13; [Epub ahead of print].

• Mitochondrial oxidative stress and epilepsy in SOD2 deficient mice: Attenuation by a lipophilic metalloporphyrin

  Liang L P, Waldbaum S, Rowley S, Huang T T, Day B J and Patel M

  Neurobiol Dis. 2011 Dec 16; [Epub ahead of print].

• Traumatic brain injury and trichloroethylene exposure interact and produce functional, histological, and mitochondrial deficits

  Sauerbeck A, Hunter R, Bing G and Sullivan P G

  Exp Neurol. 2011 Dec 20; [Epub ahead of print].

• Selective oestrogen receptor modulators differentially potentiate brain mitochondrial function

  Irwin R W, Yao J, To J, Hamilton R T, Cadenas E and Brinton R D

  J Neuroendocrinol; 2012 Jan 1. 24 (1):236-248.

• Ethanol withdrawal hastens the aging of cytochrome c oxidase

  Jung M E, Ju X, Metzger D B and Simpkins J W

  Neurobiol Aging; 2012 Mar 1. 33 (3):618.e21-32.

Technical Posters

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• Mitochondrial inhibition and oxidant production differs between pharmacologic models of Parkinson's disease

  Brian P. Dranka, Jacek Zielonka, and B. Kalyanaraman

  Society for Free Radical Biology and Medicine (SFRBM) 2011
  November 16-20, 2011
  Atlanta, GA

• Inhibition of Thioredoxin Reductase potentiates paraquat-induced mitochondrial dysfunction and neurotoxicity in N27 dopaminergic cells

  Pamela Lopert and Manisha Patel

  Society for Free Radical Biology and Medicine (SFRBM) 2011
  November 16-20, 2011
  Atlanta, GA

• Reliable in vivo measurement of mitochondrial bioenergetics in animal models of temporal lobe epilepsy

  Shane Rowley and Manisha Patel

  Society for Free Radical Biology and Medicine (SFRBM) 2011
  November 16-20, 2011
  Atlanta, GA

• Partial dependence of rotenone toxicity on mitochondrial respiration: Effects of galactose versus glucose as energy sources

  April A. Dukes and Teresa G. Hastings

  Neuroscience 2011
  November 12, 2011
  Washington DC

• Assessment of caprylic triglyceride for dietary intervention in an amyotrophic lateral sclerosis mouse model

  M. VARGHESE, W. ZHAO, P. VEMPATI, A. CHENG, G. M. PASINETTI

  Neuroscience 2011
  November 12, 2011
  Washington DC

• Preclinical efficacy of 2-Deoxyglucose to sustain mitochondrial metabolic function and delay progression of Alzheimer's pathology

  Jia YAO, Shuhua Chen, ZisuMao, Fan Ding, Enrique Cadenas, Roberta Diaz BRINTON

  Neuroscience 2011
  November 12, 2011
  Washington DC

• Mutations in ATP13A2 impact on mitochondrial function and morphology

  B. Arns, P. Seibler, A. Rakovic, A. Ramirez, C. Sue, C. Klein, A. Grünewald

  84th Congress of the German Society of Neurology (DGN)
  September 28-1, 2011
  Wiesbaden, DE

• Stimulation of mitochondrial motility in hippocampal neurons improves neurite distribution and bioenergetic capacity

  A. Ferree, A. Newby-Kew, K. Tradeau, E. Zik, V. Levy, B. Wolozin, P. Lansbury, O. Shirihai

  Mitochondrial Dynamics: From Mechanism to Disease
  September 11-15, 2011
  Sartinia, IT

• SCaMC-3, The Brain and Liver Mitochondrial ATP-Mg/Pi Transporter, Prevents Mitochondrial Damage During Excitotoxicity Insults in vitro and in vivo by

  Rueda CB, Traba J, Amigo I, Pardo B, del Arco A, Satrustegui J

  Gordon Research Conference on Calcium Signalling
  June 26-1, 2011
  Waterville Valley, ME

• The Effects of Idebenone on Mitochondrial Bioenergetics

  Valentina Giorgio, Valeria Petronilli, Anna Ghelli, Valerio Carelli, Michela Rugolo & Paolo Bernardi

  Eighth European Meeting on Mitochondrial Pathology (EuroMIT8)
  June 20-23, 2011
  Zaragoza, Spain

• DNA Damage Precedes Cell Death in Rotenone Rat Model of Parkinson's Disease

  L.H. Sanders, P. G. Mastroberardino, V. Tapias, X. Hu, C.T. Chu, J.T. Greenamyre

  Society for Free Radical Biology's 17th Annual Meeting
  November 17-20, 2010
  Orlando, FL

• Overexpression of The Neuron-Specific Drp1 Isoform that Includes Exon 3 (ISO1) Increases Mitochondrial Respiratory Capacity in Neurons

  C.A. Danilov, T. Uo, D.H. Margineantu, D. Hockenbery and R.S. Morrison

  Neuroscience 2010
  November 13-17, 2010
  San Diego, CA

• Neuronal Bioenergetic Reserves: Importance in Parkinson's Disease

  Brian P. Dranka, Anumantha G. Kanthasamy, B. Kalyanaraman

  Neuroscience 2010
  November 13-17, 2010
  San Diego, CA

• Dj-1 Knock-Down Impairs Astrocyte Mitochondrial Function

  N.J. Larsen, G. Ambrosi, S.J. Mullett, S.B. Berman, D.A. Hinkle

  Neuroscience 2010
  November 13-17, 2010
  San Diego, CA

• Decreased Respiratory Capacity and Glycolytic Rates in a Rat Model of Temporal Lobe Epilepsy Revealed by Metabolic Flux Analysis of Hippocampal Synaptosomes

  Shane Rowley and Manisha Patel

  Neuroscience 2010
  November 13-17, 2010
  San Diego, CA

• Real-Time Monitoring of Mitochondrial and Cellular Bioenergetics in Cultured Neurons in a Microplate

  Amy L. Swift, Etienne Regulier, Younga Shin, Nagendra Yadava, David Nicholls, David A. Ferrick and Min Wu

  Neuroscience 2008: Society for Neuroscience 38th Annual Meeting
  November 15-19, 2008
  Washington, DC

Webinars

Sort by: Title | Speaker | Date
• 

  XF Glycolysis Stress Test Assesses Glycolysis and Glycolytic Capacity in Cells

  Min Wu, PhD, Seahorse Bioscience
  August 30, 2011

• 

  Adaptation of Microplate-based Respirometry for Hippocampal Brain Slices

  Brian Polster, PhD, University of Maryland Medical School
  May 12, 2011

• 

  Multidimensional control of mitochondrial energy production: learning from physiology and pathology

  Rodrigue Rossignol, PhD, Université de Bordeaux
  April 27, 2011

• 

  Spare Respiratory Capacity and the Bioenergetics of the Nerve Terminal

  David Nicholls, PhD, FRSE, Buck Institute for Age Research & Lund University
  December 3, 2009

• 

  Acute Brain Injury: Assessing Mitochondrial Dysfunction and the Role of Calpain Proteases in vitro

  Brian Polster, PhD, University of Maryland Medical School
  August 19, 2009

• 

  Oxidative Stress, Mitochondrial DNA Damage and Human Disease: How mitochondria repair their genome and how to measure mtDNA repair using quantitative PCR

  Ben Van Houten, PhD, University of Pittsburgh Cancer Institute
  May 21, 2009

• 

  Cybrid Modeling of Sporadic Neurodegenerative Disorders

  Russell H. Swerdlow, MD, University of Kansas School of Medicine
  March 16, 2009

• 

  Tutorial: Measuring Bioenergetics in a Variety of Cell Types

  David Ferrick, PhD, CSO, Seahorse Bioscience
  July 17, 2008

• 

  Bioenergetic Profiling in Translational Neuroscience

  Jon Nilsen, PhD, University of Southern California
  June 25, 2008

• 

  Quantifying the Mitochondrial Proton Circuit in Intact Cells - Volts and Amps

  David G. Nicholls, PhD, FRSE, Buck Institute for Age Research
  April 29, 2008

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