NAD(P)H fluorescence transients after synaptic activity in brain slices: predominant role of mitochondrial function
Open accessAbstract
Excitatory stimulation in hippocampal slices results in biphasic NAD(P)H fluorescence transients. Previous studies using differing stimulus protocols agreed that the oxidation phase is a consequence of mitochondrial metabolism, but the reduction phase has been attributed to (1) mitochondrial nicotinamide adenine dinucleotide (NADH) generation or (2) astrocytic glycolysis triggered by glutamate uptake. In an attempt to reconcile these two views, the present study examined NAD(P)H signals evoked by a wide range of stimulus durations (40 ms to 20 secs). A combination of ionotropic glutamate receptor (iGluR) antagonists (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 2-amino-5-phosphonopentanoic acid (APV)) virtually abolished responses to brief stimuli (40 to 200 ms, 50 Hz), but a significant fraction of the signal elicited by extended stimulation (20 secs, 32 Hz) was resistant to CNQX/APV. Glycolysis was inhibited by removal of glucose and addition of 2-deoxyglucose (2DG) (10 mmol/L) or iodoacetic acid (IAA, 1 mmol/L). Pyruvate was provided as an alternative substrate for oxidative phosphorylation and the A1 receptor antagonist 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX) included to prevent decreases in synaptic efficacy. If sufficient pyruvate was supplied, responses to brief and extended stimuli were unaffected by glycolytic inhibition and not significantly reduced by an inhibitor of glucose uptake (3-O-methyl glucose, 3 mmol/L). When timed to arrive at the peak of overshoots generated by extended synaptic stimulation, brief pyruvate applications (10 mmol/L, 2 mins) had little effect on evoked NAD(P)H increases. Flavoprotein autofluorescence transients after extended stimuli matched (with inverted sign) NAD(P)H responses. Responses to extended stimuli were not reduced by a nonselective inhibitor of glutamate uptake DL-Threo-beta-benzyloxyaspartic acid (TBOA). These results suggest that NAD(P)H transients report mitochondrial dynamics, rather than recruitment of glycolytic metabolism, over a wide range of stimulus intensities.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NAD(P)H autofluorescence is almost certainly dominated by mitochondrial NADH.
“The NAD(P)H autofluorescence is almost certainly dominated by mitochondrial NADH (Brennan et al., 2006; Shuttleworth, 2010; Berndt et al., 2015).”
From Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake (2017) · cites this paper as Brennan et al., 2006
Cites
Zipfel, W. R., Williams, R. M., Christie, R. H., Nikitin, A. Y., Hyman, B. T., & Webb, W. W. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0832308100 · Cited by 1,691 · see citing works
Orkand, R. K., Nicholls, J. G., & Kuffler, S. W. (1966) · Journal of Neurophysiology · doi:10.1152/jn.1966.29.4.788 · Cited by 1,213 · see citing works
Intracellular Oxidation-Reduction States in Vivo
Chance, B., Cohen, P., Jöbsis, F. F., & Schoener, B. (1962) · Science · doi:10.1126/science.137.3529.499 · Cited by 947 · see citing works
Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis
Kasischke, K. A., Vishwasrao, H. D., Fisher, P. J., Zipfel, W. R., & Webb, W. W. (2004) · Science · doi:10.1126/science.1096485 · Cited by 742 · see citing works
Chance, B., Schoener, B., Oshino, R., Itshak, F., & Nakase, Y. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30079-0 · Cited by 679 · see citing works
SUBSTRATE SPECIFICITY OF BRAIN HEXOKINASE
Sols, A., & Crane, R. K. (1954) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)65384-0 · Cited by 599 · see citing works
Autofluorescence of viable cultured mammalian cells.
Aubin, J. E. (1979) · Journal of Histochemistry & Cytochemistry · doi:10.1177/27.1.220325 · Cited by 559 · see citing works
dl-threo-β-Benzyloxyaspartate, A Potent Blocker of Excitatory Amino Acid Transporters
Shimamoto, K., Lebrun, B., Yasuda‐Kamatani, Y., Sakaitani, M., Shigeri, Y., Yumoto, N., & Nakajima, T. (1998) · Molecular Pharmacology · doi:10.1124/mol.53.2.195 · Cited by 545 · see citing works
Matthias, K., Kirchhoff, F., Seifert, G., Hüttmann, K., Matyash, M., Kettenmann, H., & Steinhäuser, C. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-05-01750.2003 · Cited by 431 · see citing works
Ca2+-dependent changes in the mitochondrial energetics in single dissociated mouse sensory neurons
Duchen, M. R. (1992) · Biochemical Journal · doi:10.1042/bj2830041 · Cited by 338 · see citing works
Inhibition of uptake unmasks rapid extracellular turnover of glutamate of nonvesicular origin
Jabaudon, D., Shimamoto, K., Yasuda‐Kamatani, Y., Scanziani, M., Gähwiler, B. H., & Gerber, U. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.15.8733 · Cited by 305 · see citing works
Duchen, M. R., & Biscoe, T. J. (1992) · The Journal of Physiology · doi:10.1113/jphysiol.1992.sp019115 · Cited by 263 · see citing works
Flavin and Pyridine Nucleotide Oxidation-Reduction Changes in Perfused Rat Liver
Scholz, R., Thurman, R. G., WILLIAMSON, J. R., Chance, B., & Bücher, T. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)78228-3 · Cited by 254 · see citing works
Jöbsis, F. F., O’Connor, M. J., Vitale, A., & Vreman, H. J. (1971) · Journal of Neurophysiology · doi:10.1152/jn.1971.34.5.735 · Cited by 246 · see citing works
Shibuki, K., Hishida, R., Murakami, H., Kudoh, M., Kawaguchi, T., Watanabe, M., Watanabe, S., Kouuchi, T., & Tanaka, R. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.040709 · Cited by 240 · see citing works
[17] Imaging mitochondrial function in intact cells
Duchen, M. R., Surin, A. M., & Jacobson, J. (2003) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(03)61019-0 · Cited by 236 · see citing works
Regulation of mitochondrial metabolism by ER Ca 2+ release: an intimate connection
Rutter, G. A., & Rizzuto, R. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01585-1 · Cited by 208 · see citing works
Flavoprotein Autofluorescence Imaging of Neuronal Activation in the Cerebellar Cortex In Vivo
Reinert, K. C., Dunbar, R. L., Gao, W., Chen, G., & Ebner, T. J. (2004) · Journal of Neurophysiology · doi:10.1152/jn.01275.2003 · Cited by 172 · see citing works
Fitzjohn, S. M., Bortolotto, Z. A., Palmer, M. J., Doherty, A., Ornstein, P. L., Schoepp, D. D., Kingston, A. E., Lodge, D., & Collingridge, G. L. (1998) · Neuropharmacology · doi:10.1016/s0028-3908(98)00145-2 · Cited by 159 · see citing works
NAD(P)H fluorescence imaging of postsynaptic neuronal activation in murine hippocampal slices
Shuttleworth, C. W., Brennan, A. M., & Connor, J. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03196.2003 · Cited by 151 · see citing works
McCormack, J. G., & Denton, R. M. (1994) · Developmental Neuroscience · doi:10.1159/000111332 · Cited by 150 · cited 2× · see citing works
“Excitatory stimulation in hippocampal slices results in biphasic NAD(P)H fluorescence transients.”
BackgroundChan, S. L., Griffin, W. S. T., & Mattson, M. P. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990801)57:3 · Cited by 137 · see citing works
Wu, K. M., Aoki, C. J., Elste, A. M., Rogalski, A. A., & Siekevitz, P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.13273 · Cited by 116 · see citing works
Pellerin, L., & Magistretti, P. J. (2004) · Science · doi:10.1126/science.1100428 · Cited by 115 · see citing works
NADH fluorescence and [K+]o changes during hippocampal electrical stimulation
Lewis, D. V., & Schuette, W. H. (1975) · Journal of Neurophysiology · doi:10.1152/jn.1975.38.2.405 · Cited by 104 · see citing works
Johnson, B. G., Wright, R. A., Arnold, M. B., Wheeler, W. J., Ornstein, P. L., & Schoepp, D. D. (1999) · Neuropharmacology · doi:10.1016/s0028-3908(99)00053-2 · Cited by 101 · see citing works
Kann, O., Schuchmann, S., Buchheim, K., & Heinemann, U. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00026-5 · Cited by 98 · see citing works
Obeidat, A. S., Jarvis, C. R., & Andrew, R. D. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200002000-00024 · Cited by 92 · see citing works
Foster, K. A., Beaver, C. J., & Turner, D. A. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.01.040 · Cited by 78 · see citing works
Mironov, S. L., & Richter, D. W. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0227b.x · Cited by 78 · see citing works
Effects of membrane depolarization on nicotinamide nucleotide fluorescence in brain slices
Lipton, P. (1973) · Biochemical Journal · doi:10.1042/bj1360999 · Cited by 78 · see citing works
Schuchmann, S., Kovacs, R., Kann, O., Heinemann, U., & Buchheim, K. (2001) · Brain Research Protocols · doi:10.1016/s1385-299x(01)00080-0 · Cited by 75 · see citing works
A Depletable Pool of Adenosine in Area CA1 of the Rat Hippocampus
Pearson, T., Nuritova, F., Caldwell, D., Dale, N., & Frenguelli, B. G. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-07-02298.2001 · Cited by 73 · see citing works
Roles of Metabotropic Glutamate Receptors in Brain Plasticity and Pathology
Miller, S., Kesslak, J. P., Romano, C., & Cotman, C. W. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb17506.x · Cited by 65 · see citing works
Bachelard, H. S., COX, D. W. G., & Drower, J. (1984) · The Journal of Physiology · doi:10.1113/jphysiol.1984.sp015279 · Cited by 60 · see citing works
Hermans, E., Challiss, R. A. J., & Nahorski, S. R. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702359 · Cited by 54 · see citing works
Mitochondrial NADH Redox State, Monitoring Discovery and Deployment in Tissue
Chance, B. (2004) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(04)85020-1 · Cited by 50 · see citing works
Strong, A. J., Harland, S. P., Meldrum, B. S., & Whittington, D. J. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199605000-00003 · Cited by 50 · see citing works
Coelho, J. E., de Mendonça, A., & Ribeiro, J. A. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02381-7 · Cited by 48 · see citing works
Murakami, H., Kamatani, D., Hishida, R., Takao, T., Kudoh, M., Kawaguchi, T., Tanaka, R., & Shibuki, K. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03237.x · Cited by 40 · see citing works
Glutamate release increases during mossy‐CA3 LTP but not during Schaffer‐CA1 LTP
Kawamura, Y., Manita, S., Nakamura, T., Inoue, M., Kudo, Y., & Miyakawa, H. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03258.x · Cited by 40 · see citing works
Laurel, H., Heller, H. C., & van den Pol, A. N. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-05-01825.1997 · Cited by 40 · see citing works
Guo, Z., Lee, J., Lane, M. A., & Mattson, M. P. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00564.x · Cited by 37 · see citing works
Functional integration of the transport of ammonium, glutamate and glutamine in astrocytes
Brookes, N. (2000) · Neurochemistry International · doi:10.1016/s0197-0186(00)00015-2 · Cited by 33 · see citing works
Zhao, Y.-T., Tekkök, S. B., & Krnjević, K. (1997) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-75-5-368 · Cited by 32 · see citing works
Brauser, B., Bücher, T., & Dolivo, M. (1970) · FEBS Letters · doi:10.1016/0014-5793(70)80291-5 · Cited by 28 · see citing works
Optical Methods for Probing Mitochondrial Function in Brain Slices
Sick, T. J., & Pérez‐Pinzón, M. A. (1999) · Methods · doi:10.1006/meth.1999.0763 · Cited by 27 · see citing works
Mayevsky, A., Nioka, S., & Chance, B. (1988) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-9510-6_43 · Cited by 20 · see citing works
Kinetic Model of 2-Deoxyglucose Metabolism Using Brain Slices
Newman, G. C., Hospod, F. E., & Patlak, C. S. (1990) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1990.93 · Cited by 19 · see citing works
[12] Functional imaging of mitochondrial redox state
Kunz, D., Winkler, K., Elger, C. E., & Kunz, W. S. (2002) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(02)52014-0 · Cited by 16 · see citing works
Izumi, Y., Benz, A. M., Katsuki, H., Matsukawa, M., Clifford, D. B., & Zorumski, C. F. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00661-9 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Synaptic Energy Use and Supply
Harris, J. J., Jolivet, R., & Attwell, D. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.019 · Cited by 1,747 · see citing works
Mitochondria and neuronal activity
Kann, O., & Kovács, R. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00222.2006 · Cited by 847 · see citing works
Microglia monitor and protect neuronal function through specialized somatic purinergic junctions
Cserép, C., Pósfai, B., Lénárt, N., Fekete, R., László, Z. I., Lele, Z., Orsolits, B., Molnár, G., Heindl, S., Schwarcz, A. D., et al. (2020) · Science · doi:10.1126/science.aax6752 · Cited by 684 · see citing works
Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature
Ayata, C., & Lauritzen, M. (2015) · Physiological Reviews · doi:10.1152/physrev.00027.2014 · Cited by 555 · see citing works
Brain lactate metabolism: the discoveries and the controversies
Dienel, G. A. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.175 · Cited by 479 · see citing works
Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake
Díaz-García, C. M., Mongeon, R., Lahmann, C., Koveal, D., Zucker, H., & Yellen, G. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.021 · Cited by 466 · see citing works
“…of astrocytes (Kasischke et al., 2004), it is almost certainly due instead to replenishment of mitochondrial NADH in neurons bymultiplemeans (Brennan et al., 2006; Shuttleworth, 2010; Berndt et al., 2015): stimulation of tricarboxylic acid cycle dehydrogenases by calcium as well as…”
Hall, C. N., Klein-Flugge, M. C., Howarth, C., & Attwell, D. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0026-12.2012 · Cited by 451 · see citing works
Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism
Yellen, G. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201803152 · Cited by 371 · see citing works
“…of NADH than cytosol, and because of the higher fluorescence of protein-bound NADH, mitochondrial NADH is considered to be the major source of the NAD(P)H signal (though this is contested; see Kasischke et al., 2004; Brennan et al., 2006; Blacker et al., 2014; and the discussion below).”
BackgroundResultInfluentialMetabolic signaling by lactate in the brain
Barros, L. F. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.04.002 · Cited by 326 · see citing works
Kann, O., Papageorgiou, I. E., & Draguhn, A. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.104 · Cited by 295 · see citing works
Liu, D., Gharavi, R. B., PITTA, M. G. R., Gleichmann, M., & Mattson, M. P. (2009) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8058-1 · Cited by 248 · see citing works
Figley, C. R., & Stroman, P. W. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07584.x · Cited by 232 · see citing works
Imaging Mitochondrial Flux in Single Cells with a FRET Sensor for Pyruvate
San Martín, A., Ceballo, S., Baeza-Lehnert, F., Lerchundi, R., Valdebenito, R., Contreras-Baeza, Y., Alegría, K., & Barros, L. F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085780 · Cited by 197 · see citing works
Long, A. N., Owens, K., Schlappal, A. E., Kristián, T., Fishman, P. S., & Schuh, R. A. (2015) · BMC Neurology · doi:10.1186/s12883-015-0272-x · Cited by 198 · see citing works
Kann, O., Huchzermeyer, C., Kovács, R., Wirtz, S., & Schuelke, M. (2011) · Brain · doi:10.1093/brain/awq333 · Cited by 189 · see citing works
Hirrlinger, J., & Dringen, R. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2009.10.003 · Cited by 171 · see citing works
High resolution measurement of the glycolytic rate
Bittner, C. X. (2010) · Frontiers in Neuroenergetics · doi:10.3389/fnene.2010.00026 · Cited by 151 · see citing works
Shen, Y., Kapfhamer, D., Minnella, A. M., Kim, J.-E., Won, S. J., Chen, Y., Huang, Y., Low, L. H., Massa, S. M., & Swanson, R. A. (2017) · Nature Communications · doi:10.1038/s41467-017-00707-0 · Cited by 133 · see citing works
Park, J. H., Long, A. N., Owens, K., & Kristián, T. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.07.018 · Cited by 121 · see citing works
NAD+ and NADH in brain functions, brain diseases and brain aging
Ying, W. (2006) · Frontiers in bioscience · doi:10.2741/2194 · Cited by 122 · see citing works
Huchzermeyer, C., Albus, K., Gabriel, H.-J., Otáhal, J., Taubenberger, N., Heinemann, U., Kovács, R., & Kann, O. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4105-07.2008 · Cited by 115 · see citing works
Preventing NAD+ Depletion Protects Neurons against Excitotoxicity
Liu, D., PITTA, M. G. R., & Mattson, M. P. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.028 · Cited by 114 · see citing works
Ward, M. W., Huber, H. J., Weisová, P., Düßmann, H., Nicholls, D. G., & Prehn, J. H. M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1984-07.2007 · Cited by 114 · see citing works
Ivanov, A. I., Malkov, A. E., Waseem, T., Mukhtarov, M., Buldakova, S., Gubkina, O., Zilberter, M., & Zilberter, Y. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.222 · Cited by 113 · see citing works
Shuttleworth, C. W. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2009.12.015 · Cited by 104 · see citing works
Unraveling the complex metabolic nature of astrocytes
Bouzier-Sore, A.-K., & Pellerin, L. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00179 · Cited by 134 · see citing works
Jolivet, R., Coggan, J. S., Allaman, I., & Magistretti, P. J. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004036 · Cited by 105 · see citing works
Mitochondrial NADH Fluorescence Is Enhanced by Complex I Binding
Blinova, K., Levine, R. L., Boja, E. S., Griffiths, G. L., Shi, Z., Ruddy, B. M., & Balaban, R. S. (2008) · Biochemistry · doi:10.1021/bi800307y · Cited by 100 · see citing works
Nicotinamide mononucleotide alters mitochondrial dynamics by SIRT3‐dependent mechanism in male mice
Klimova, N., Long, A. N., & Kristián, T. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24397 · Cited by 97 · see citing works
Aubert, A., Pellerin, L., Magistretti, P. J., & Costalat, R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605864104 · Cited by 97 · see citing works
Díaz‐García, C. M., Meyer, D. J., Nathwani, N., Rahman, M., Martínez‐François, J. R., & Yellen, G. (2021) · eLife · doi:10.7554/elife.64821 · Cited by 95 · see citing works
Lourenço, C. F., Ledo, A., Barbosa, R. M., & Laranjinha, J. A. N. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.04.026 · Cited by 99 · see citing works
Synaptic activity controls localization and function of CtBP1 via binding to Bassoon and Piccolo
Ivanova, D., Dirks, A., Montenegro‐Venegas, C., Schöne, C., Altrock, W. D., Marini, C., Frischknecht, R., Schanze, D., Zenker, M., Gundelfinger, E. D., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201488796 · Cited by 86 · see citing works
Springett, R., & Swartz, H. M. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1620 · Cited by 85 · see citing works
Barros, L. F., Courjaret, R. J., Jakoby, P., Loaiza, A., Lohr, C., & Deitmer, J. W. (2008) · Glia · doi:10.1002/glia.20820 · Cited by 83 · see citing works
Astrocytic Calcium Signaling: Mechanism and Implications for Functional Brain Imaging
Wang, X., Takano, T., & Nedergaard, M. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-543-5_5 · Cited by 75 · see citing works
Schurr, A. (2011) · Frontiers in Pharmacology · doi:10.3389/fphar.2011.00096 · Cited by 73 · see citing works
Flavoprotein autofluorescence imaging in the cerebellar cortex in vivo
Reinert, K. C., Gao, W., Chen, G., & Ebner, T. J. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21348 · Cited by 69 · see citing works
Chennakesavan, K., Periyasamy, S., Jayachandran, K. S., & Anusuyadevi, M. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00028 · Cited by 67 · see citing works
The micro-architecture of the cerebral cortex: Functional neuroimaging models and metabolism
Riera, J. J., Schousboe, A., Waagepetersen, H. S., Howarth, C., & Hyder, F. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2007.12.051 · Cited by 63 · see citing works
Kim, J.-E., Kim, Y., Kim, J. Y., & Kang, T.-C. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.331 · Cited by 57 · see citing works
Glycolysis selectively shapes the presynaptic action potential waveform
Lujan, B., Kushmerick, C., Banerjee, T. D., Dagda, R. K., & Renden, R. (2016) · Journal of Neurophysiology · doi:10.1152/jn.00629.2016 · Cited by 56 · see citing works
Single-cell imaging tools for brain energy metabolism: a review
Martín, A. S., Sotelo-Hitschfeld, T., Lerchundi, R., Fernández‐Moncada, I., Ceballo, S., Valdebenito, R., Baeza‐Lehnert, F., Alegría, K., Contreras‐Baeza, Y., Garrido-Gerter, P., et al. (2014) · Neurophotonics · doi:10.1117/1.nph.1.1.011004 · Cited by 57 · see citing works
Ivanov, A., Mukhtarov, M. R., Bregestovski, P. D., & Zilberter, Y. (2011) · Frontiers in Neuroenergetics · doi:10.3389/fnene.2011.00002 · Cited by 55 · see citing works
Wang, X., Chen, G., Gao, W., & Ebner, T. J. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00717.2010 · Cited by 54 · see citing works
Bi, J., Li, H., Ye, S. Q., & Ding, S. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07566.x · Cited by 51 · see citing works
Energy demand of synaptic transmission at the hippocampal Schaffer-collateral synapse
Liotta, A., Rösner, J., Huchzermeyer, C., Wojtowicz, A., Kann, O., Schmitz, D., Heinemann, U., & Kovács, R. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.116 · Cited by 48 · see citing works
The Energy Demand of Fast Neuronal Network Oscillations: Insights from Brain Slice Preparations
Kann, O. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2011.00090 · Cited by 51 · see citing works
Kristián, T., Balan, I. S., Schuh, R. A., & Onken, M. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22626 · Cited by 47 · see citing works
Xie, M., Wang, W., Kimelberg, H. K., & Zhou, M. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600545 · Cited by 48 · see citing works
Gandhi, G. K., Cruz, N. F., Ball, K. K., Theus, S. A., & Dienel, G. A. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06173.x · Cited by 47 · see citing works
Abnormal NMDA receptor function exacerbates experimental autoimmune encephalomyelitis
Grasselli, G., Rossi, S., Musella, A., Gentile, A., Loizzo, S., Muzio, L., Sanza, C. D., Errico, F., Musumeci, G., Haji, N., et al. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.02178.x · Cited by 47 · see citing works
Won, S. J., Yoo, B. H., Brennan, A. M., Shin, B. S., Kauppinen, T. M., Berman, A., Swanson, R. A., & Suh, S. W. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2084-10.2010 · Cited by 47 · see citing works
Wang, X., Chen, G., Gao, W., & Ebner, T. J. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.01.071 · Cited by 45 · see citing works
Reyes, R. C., Cittolin‐Santos, G. F., Kim, J.-E., Won, S. J., Brennan, A., Katz, M., Glass, G. A., & Swanson, R. A. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0404-4 · Cited by 45 · see citing works
Turner, D. A., Foster, K. A., Galeffi, F., & Somjen, G. G. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.06.001 · Cited by 45 · see citing works
Dienel, G. A., & Cruz, N. F. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.011 · Cited by 43 · see citing works
Crosstalk of Signaling and Metabolism Mediated by the NAD+/NADH Redox State in Brain Cells
Winkler, U., & Hirrlinger, J. (2015) · Neurochemical Research · doi:10.1007/s11064-015-1526-0 · Cited by 43 · see citing works
Cellular and Metabolic Origins of Flavoprotein Autofluorescence in the Cerebellar Cortex in vivo
Reinert, K. C., Gao, W., Chen, G., Wang, X., Peng, Y.-P., & Ebner, T. J. (2011) · The Cerebellum · doi:10.1007/s12311-011-0278-x · Cited by 40 · see citing works
Neuron-Specific Conditional Expression of a Mitochondrially Targeted Fluorescent Protein in Mice
Chandrasekaran, K., Hazelton, J. L., Wang, Y., Fiskum, G. M., & Kristián, T. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4191-06.2006 · Cited by 38 · see citing works
NBCe1 mediates the regulation of the NADH/NAD+redox state in cortical astrocytes by neuronal signals
Köhler, S., Winkler, U., Sicker, M., & Hirrlinger, J. (2018) · Glia · doi:10.1002/glia.23504 · Cited by 35 · see citing works
Energy and Potassium Ion Homeostasis during Gamma Oscillations
Kann, O., Hollnagel, J., Elzoheiry, S., & Schneider, J. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00047 · Cited by 33 · see citing works
Galeffi, F., Foster, K. A., Sadgrove, M. P., Beaver, C. J., & Turner, D. A. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04939.x · Cited by 32 · see citing works
Epileptic Focus and Alteration of Metabolism
Otáhal, J., Folbergrová, J., Kovacs, R., Kunz, W. S., & Maggio, N. (2014) · International review of neurobiology · doi:10.1016/b978-0-12-418693-4.00009-1 · Cited by 29 · see citing works
Mukhtarov, M. R., Ivanov, A., Zilberter, Y., & Bregestovski, P. D. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07111.x · Cited by 23 · see citing works
Effects of relative hypoglycemia on LTP and NADH imaging in rat hippocampal slices
Sadgrove, M. P., Beaver, C. J., & Turner, D. A. (2007) · Brain Research · doi:10.1016/j.brainres.2007.06.052 · Cited by 23 · see citing works
Lujan, B., Singh, M., Singh, A., & Renden, R. (2021) · Journal of Neurophysiology · doi:10.1152/jn.00333.2021 · Cited by 21 · see citing works
Modulation of the amplitude of NAD(P)H fluorescence transients after synaptic stimulation
Brennan, A. M., Connor, J. A., & Shuttleworth, C. W. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21288 · Cited by 19 · see citing works
L’Heureux, B., Gurden, H., & Pain, F. (2009) · Optics Express · doi:10.1364/oe.17.009477 · Cited by 18 · see citing works
Gordon, G. R., Howarth, C., & MacVicar, B. A. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-1-4899-7678-9_15 · Cited by 17 · see citing works
Kann, O., Taubenberger, N., Huchzermeyer, C., Papageorgiou, I. E., Benninger, F., Heinemann, U., & Kovács, R. (2011) · Cell Calcium · doi:10.1016/j.ceca.2011.10.004 · Cited by 16 · see citing works
Loizzo, S., Pieri, M., Ferri, A., Carrı̀, M. T., Zona, C., Fortuna, A., & Vella, S. (2009) · Mitochondrion · doi:10.1016/j.mito.2009.11.001 · Cited by 16 · see citing works
Energy Metabolism in the Brain
Dienel, G. A. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397179-1.00003-8 · Cited by 16 · see citing works
Minimizing photodecomposition of flavin adenine dinucleotide fluorescence by the use of pulsed LEDs
Rösner, J., Liotta, A., Angamo, E. A., Spies, C., Heinemann, U., & KOVÁCS, R. (2016) · Journal of Microscopy · doi:10.1111/jmi.12436 · Cited by 16 · see citing works
Lactate Fuels the Neonatal Brain
Kasischke, K. A. (2011) · Frontiers in Neuroenergetics · doi:10.3389/fnene.2011.00004 · Cited by 15 · see citing works
Hamann, M., Richter, A., Fink, H., & Rex, A. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21891 · Cited by 10 · see citing works
Chen, G., Carter, R. E., Cleary, J. D., Reid, T. S., Ranum, L. P. W., Swanson, M. S., & Ebner, T. J. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.01.003 · Cited by 9 · see citing works
Oleic acid enhances the production of reactive oxygen species in neuronal tissue
Alves, J. L., Figueira, A. S. C., Souto, M., Lopes, I. L., Dionı́sio, J. C., Quinta-Ferreira, R. M., & Quinta-Ferreira, M. E. (2020) · Energy Reports · doi:10.1016/j.egyr.2019.11.034 · Cited by 8 · see citing works
Schwarz, K., & Schmitz, F. (2017) · Biochemical Journal · doi:10.1042/bcj20160886 · Cited by 6 · see citing works
Glutamate-induced metabolic changes influence the cytoplasmic redox state of hippocampal neurons
Porras, O. H., & Stutzin, A. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.06.097 · Cited by 6 · see citing works
Metabolic response of auditory brainstem neurons to their broad physiological activity range
Palandt, N., Resch, C., Unterlechner, P., Voshagen, L., Winhart, V. R., & Kunz, L. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16091 · Cited by 5 · see citing works
Monitoring of Cellular Dynamics with Electrochemical Detection Techniques
Heiskanen, A. R., & Emnéus, J. (2011) · Modern aspects of electrochemistry · doi:10.1007/978-1-4614-0347-0_1 · Cited by 5 · see citing works
Astrocyte control of blood flow
Gordon, G. R., Mulligan, S. J., & MacVicar, B. A. (2008) · Springer eBooks · doi:10.1007/978-0-387-79492-1_18 · Cited by 5 · see citing works
Cserép, C., Pósfai, B., Orsolits, B., Molnár, G., Heindl, S., Lénárt, N., Fekete, R., László, Z. I., Lele, Z., Schwarcz, A. D., et al. (2019) · SSRN Electronic Journal · doi:10.2139/ssrn.3339900 · Cited by 4 · see citing works
Intraoperative Optical Imaging
Frostig, R. (2002) · CRC Press eBooks · doi:10.1201/9781420038491-12 · Cited by 3 · see citing works
Uytingco, C. R., Puché, A. C., & Munger, S. D. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165342 · Cited by 3 · see citing works
Gray, J., Halemirle, G., Ferrán, B., Rose, H., Redwine, T. L., Pham, S., Hagy, B., Pranay, A., Giorgione, J. R., Hussong, S. A., et al. (2025) · The Journal of Physiology · doi:10.1113/jp287618 · Cited by 2 · see citing works
The impact of dendritic mitochondrial heterogeneity on synapse function
Cawley, M. L., & Farris, S. (2026) · Trends in Neurosciences · doi:10.1016/j.tins.2026.01.011 · Cited by 1 · see citing works
Optical Approaches to Study Metabolic Consequences of Spreading Depression In Vivo
Shuttleworth, C. W. (2011) · Advances in neurobiology · doi:10.1007/978-1-4614-1788-0_12
Relative contributions of zinc and calcium to acute injury to hippocampal CA1 neurons
Dietz, R. M. (2010) · UNM’s Digital Repository (University of New Mexico)
Glucose Metabolism During Neural Activation
Fillenz, M. (2011) · Advances in neurobiology · doi:10.1007/978-1-4614-1788-0_21
Visible Light Optical Imaging and Spectroscopy during Neurosurgery
Allahabadi, S., Jia, C., & Prakash, N. (2016) · CRC Press eBooks · doi:10.1201/9781315373058-17
Mathematical Model of Hippocampal Microdialysis: Validation of in vivo MethodologyPreprint
Vinciguerra, D. A., Vigeant, M. A.-S., & McNay, E. C. (2020) · arXiv (Cornell University) · doi:10.48550/arxiv.2011.06662
Bastos, F. C., Matias, C. M., Lopes, I. O., Vieira, J. P. P., Santos, R. M., Rosário, L. M., Quinta-Ferreira, R. M., & Quinta-Ferreira, M. E. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.100898
Reis, P. M., Ribeiro-Alves, J. L., Matias, C. M., Santos, A. D., Castro, L. M., Quinta-Ferreira, M. E., Gando‐Ferreira, L. M., & Quinta-Ferreira, R. M. (2026) · Journal of Water Process Engineering · doi:10.1016/j.jwpe.2026.110484
A study of selective vulnerability to diabetes of nerves supplying the ileum using in vitro models
Voukali, E. (2013) · UCL Discovery (University College London)
Metabolic flux analysis of neural cell metabolism in primary cultures
Amaral, A. I. (2011) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
- Authors
- Brennan, A. M., Connor, J. A., & Shuttleworth, C. W.
- Affiliations
- University of New Mexico (US)
- Corresponding author
- Shuttleworth, C William
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2006-11
- Volume
- 26
- Issue
- 11
- Pages
- 1389-1406
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W2026777646
- Cited by
- 97
- References
- 51
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 6 · 2013: 4 · 2012: 5
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS43458, R01NS043458)
- National Center for Research Resources (RR-15636, P20RR015636)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- mitochondrial metabolism, hippocampus, synaptic activity, glutamate uptake, ionotropic glutamate receptors, pyruvate, 2-deoxyglucose, 3-O-methylglucose, DPCPX, CNQX, APV, TBOA
- MeSH terms
- Animals, Bicuculline, Brain, Electric Stimulation, Flavoproteins, Fluorescence, Glycolysis, Male, Mice, Inbred C57BL, Mitochondria, NADP, Neuroglia, Neurons, Pyruvates, Synapses, 2-Amino-5-phosphonovalerate, Long-Term Potentiation, Excitatory Amino Acid Antagonists, Glutamic Acid, 6-Cyano-7-nitroquinoxaline-2,3-dione, GABA Antagonists, Excitatory Postsynaptic Potentials, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
