Skip to main content
Log in

Differentiated effect of ageing on the enzymes of Krebs’ cycle, electron transfer complexes and glutamate metabolism of non-synaptic and intra-synaptic mitochondria from cerebral cortex

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

The effect of ageing on the activity of enzymes linked to Krebs’ cycle, electron transfer chain and glutamate metabolism was studied in three different types of mitochondria of cerebral cortex of 1-year old and 2-year old male Wistar rats. We assessed the maximum rate (Vmax) of the mitochondrial enzyme activities in non-synaptic perikaryal mitochondria, and in two populations of intra-synaptic mitochondria. The results indicated that: (i) in normal, steady-state cerebral cortex the values of the catalytic activities of the enzymes markedly differed in the various populations of mitochondria; (ii) in intra-synaptic mitochondria, ageing affected the catalytic properties of the enzymes linked to Krebs’ cycle, electron transfer chain and glutamate metabolism; (iii) these changes were more evident in intra-synaptic “heavy” than “light” mitochondria. These results indicate a different age-related vulnerability of subpopulations of mitochondria in vivo located into synapses than non-synaptic ones.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • BAC Ackrell EB Kearney TP Singer (1978) Mammalian succinate dehydrogenase RW Estabrook ME Pullman (Eds) Methods in Enzymology NumberInSeries23 Academic Press New York and London 446–483

    Google Scholar 

  • A Battino A Gorini RF Villa ML Genova C Bovina S Sassi GP Littarru G Lenaz (1995) ArticleTitleCoenzyme Q content in synaptic and non-synaptic mitochondria from different brain regions in the ageing rat Mech Ageing Develop 78 173–187 Occurrence Handle1:CAS:528:DyaK2MXmtFajtLo%3D Occurrence Handle10.1016/0047-6374(94)01535-T

    Article  CAS  Google Scholar 

  • M Battino E Bertoli G Formiggini S Sassi A Gorini RF Villa G Lenaz (1991) ArticleTitleStructural and functional aspects of the respiratory chain of synaptic and non-synaptic mitochondria derived from selected brain regions J Bioenerg Biomembr 23 345–363 Occurrence Handle1646801 Occurrence Handle1:CAS:528:DyaK3MXit1Kltbg%3D Occurrence Handle10.1007/BF00762227

    Article  PubMed  CAS  Google Scholar 

  • M Battino GP Littarru A Gorini RF Villa (1996) ArticleTitleCoenzyme Q, peroxidation and cytochrome oxidase features after Parkinson’s-like disease by MPTP toxicity in intra-synaptic and non-synaptic mitochondria from Macaca fascicularis cerebral cortex and hippocampus: action of diidroergocriptine Neurochem Res 21 1505–1514 Occurrence Handle8953566 Occurrence Handle1:CAS:528:DyaK28XnsVCku7k%3D

    PubMed  CAS  Google Scholar 

  • M Battino JL Quiles JR Hurtas JF Mataix A Gorini RF Villa (2000) ArticleTitleCerebral cortex synaptic heavy mitochondria may represent the oldest synaptic mitochondrial population: biochemical heterogeneity and effects of L-acetylcarnitine J Bioenerg Biomembr 32 163–173 Occurrence Handle11768749 Occurrence Handle1:CAS:528:DC%2BD3cXlt1ansr8%3D Occurrence Handle10.1023/A:1005559930210

    Article  PubMed  CAS  Google Scholar 

  • M Battino S Bompadre L Leone RF Villa A Gorini (2001) ArticleTitleCoenzyme Q9 and Q10, Vitamin E and peroxidation in rat synaptic and non-synaptic occipital cerebral cortex mitochondria during ageing Biol Chem 382 925–931 Occurrence Handle11501757 Occurrence Handle1:CAS:528:DC%2BD3MXmsFKhsrk%3D Occurrence Handle10.1515/BC.2001.115

    Article  PubMed  CAS  Google Scholar 

  • M Battino MS Ferreiro GP Littarru JL Quiles MC Ramirez-Tortosa JR Huertas JF Mataix RF Villa A Gorini (2002) ArticleTitleStructural damages induced by peroxidation could account for functional impairment of heavy synaptic mitochondria Free Rad Res 36 479–484 Occurrence Handle1:CAS:528:DC%2BD38XotFGmsLs%3D Occurrence Handle10.1080/10715760290021351

    Article  CAS  Google Scholar 

  • G Benzi A Moretti (1995) ArticleTitleAge- and peroxidative stress-related modifications of the cerebral enzymatic activities linked to mitochondria and the glutatione system Free Radic Biol Med 17 77–101 Occurrence Handle10.1016/0891-5849(94)00244-E

    Article  Google Scholar 

  • HU Bergmeyer E Bernt (1974) Glutamate-pyruvate-transaminase HU Bergmeyer (Eds) Methods of Enzymatic Analysis NumberInSeries2 Academic Press New York and London 752–758

    Google Scholar 

  • JP Blass (2000) ArticleTitleThe mitochondrial spiral. An adequate cause of dementia in the Alzheimer’s syndrome Ann NY Acad Sci 924 170–183 Occurrence Handle11193795 Occurrence Handle1:CAS:528:DC%2BD3MXntVeisg%3D%3D Occurrence Handle10.1111/j.1749-6632.2000.tb05576.x

    Article  PubMed  CAS  Google Scholar 

  • JP Blass RK Sheu JM Cederbaum (1988) ArticleTitleEnergy metabolism in disorders of the nervous system Rev Neurol (Paris) 144 543–563 Occurrence Handle1:STN:280:DyaL1M%2FlvVehtQ%3D%3D

    CAS  Google Scholar 

  • MD Brand (2000) ArticleTitleUncoupling to survive? The role of mitochondrial inefficiency in ageing Exp Gerontol 35 811–820 Occurrence Handle11053672 Occurrence Handle1:CAS:528:DC%2BD3cXot1Wqtrs%3D Occurrence Handle10.1016/S0531-5565(00)00135-2

    Article  PubMed  CAS  Google Scholar 

  • N Dahlgren M Ingvar H Yokoyama BK Siesjö (1981) ArticleTitleInfluence of nitrous oxide on local cerebral blood flow in awake, minimally restrained rats J Cereb Blood Flow Metab 1 211–218 Occurrence Handle6799529 Occurrence Handle1:CAS:528:DyaL38XhtFOisLo%3D

    PubMed  CAS  Google Scholar 

  • ML Genova C Bovina M Marchetti F Pallotti C Tietz G Biagini A Pugnaloni C Viticchi A Gorini RF Villa G Lenaz (1997) ArticleTitleDecrease of rotenone inhibition is a sensitive parameter of complex I damage in brain non-synaptic mitochondria of aged rats FEBS Lett 410 467–469 Occurrence Handle9237684 Occurrence Handle1:CAS:528:DyaK2sXktlCqtrc%3D Occurrence Handle10.1016/S0014-5793(97)00638-8

    Article  PubMed  CAS  Google Scholar 

  • E Gnaiger B Lassnig AV Kuznetsov R Margreiter (1998) ArticleTitleMitochondrial respiration in the low oxygen environment of the cell. Effect of ADP on oxygen kinetics Biochim Biophys Acta 1365 249–254 Occurrence Handle9693739 Occurrence Handle1:CAS:528:DyaK1cXksFKitr4%3D Occurrence Handle10.1016/S0005-2728(98)00076-0

    Article  PubMed  CAS  Google Scholar 

  • A Gorini A D’Angelo RF Villa (1998) ArticleTitleAction of L-Acetylcarnitine on different cerebral mitochondrial populations from cerebral cortex Neurochem Res 23 1485–1491 Occurrence Handle9821151 Occurrence Handle1:CAS:528:DyaK1cXntlaqur0%3D Occurrence Handle10.1023/A:1020907400905

    Article  PubMed  CAS  Google Scholar 

  • A Gorini A D’Angelo RF Villa (1999) ArticleTitleEnergy metabolism of synaptosomal subpopulations from different neuronal systems of rat hippocampus: effect of L-acetylcarnitine administration in vivo Neurochem Res 24 617–624 Occurrence Handle10344589 Occurrence Handle1:CAS:528:DyaK1MXjtVantr0%3D Occurrence Handle10.1023/A:1021008306414

    Article  PubMed  CAS  Google Scholar 

  • JR Harp L Nilsson BK Siesjö (1976) ArticleTitleThe effect of halothane anesthesia upon cerebral oxygen consumption in the rat Acta Anaesthesiologica Scand 20 83–90 Occurrence Handle1:CAS:528:DyaE28Xkt1yksLs%3D

    CAS  Google Scholar 

  • CF Hollander MJ van Zwieten C Zurcher (1983) The aged animal WH Gispen J Traber (Eds) Aging of the Brain Elsevier Amsterdam 187–196

    Google Scholar 

  • S Hoyer (1985) ArticleTitleThe effect of age on glucose and energy metabolism in brain cortex of rats Arch Gerontol Geriatr 4 193–203 Occurrence Handle4074019 Occurrence Handle1:CAS:528:DyaL28XjvVan Occurrence Handle10.1016/0167-4943(85)90001-9

    Article  PubMed  CAS  Google Scholar 

  • S Hoyer (1988) ArticleTitleGlucose and related brain metabolism in normal aging Age 11 150–156 Occurrence Handle1:CAS:528:DyaL1MXntlWnug%3D%3D Occurrence Handle10.1007/BF02432295

    Article  CAS  Google Scholar 

  • S Hoyer (1995) ArticleTitleAge-related changes in cerebral oxidative metabolism. Implications for drug therapy Drugs & Aging 6 210–218 Occurrence Handle1:STN:280:DyaK2MzksFGrug%3D%3D

    CAS  Google Scholar 

  • S Hoyer (2002) ArticleTitleThe aging brain. Changes in the neuronal insulin/insulin receptor signal transduction cascade trigger late-onset sporadic Alzheimer disease (SAD). A mini review J Neural Transm 109 991–1002 Occurrence Handle12111436 Occurrence Handle1:CAS:528:DC%2BD38XnsFOis7Y%3D Occurrence Handle10.1007/s007020200082

    Article  PubMed  CAS  Google Scholar 

  • S Hoyer C Krier (1986) ArticleTitleIschemia and the aging brain. Studies on glucose and energy metabolism in rat cerebral cortex Neurobiol Aging 7 23–29 Occurrence Handle3951656 Occurrence Handle1:CAS:528:DyaL28XhtVOgt7Y%3D Occurrence Handle10.1016/0197-4580(86)90022-9

    Article  PubMed  CAS  Google Scholar 

  • S Hoyer H Lannert E Latteier T Meisel (2004) ArticleTitleRelationship between cerebral energy metabolism in parietotemporal cortex and hippocampus and mental activity during aging in rats J Neural Transm 111 575–589 Occurrence Handle15088151 Occurrence Handle1:CAS:528:DC%2BD2cXjtFyit7c%3D Occurrence Handle10.1007/s00702-004-0126-y

    Article  PubMed  CAS  Google Scholar 

  • M Ingvar BK Siesjö (1982) ArticleTitleEffects of nitrous oxide on local cerebral glucose utilization in rats J Cereb Blood Flow Metab 2 481–486 Occurrence Handle7142311 Occurrence Handle1:CAS:528:DyaL3sXks1yltw%3D%3D

    PubMed  CAS  Google Scholar 

  • JCK Lai JM Walsh SC Dennis JB Clark (1977) ArticleTitleSynaptic and non-synaptic mitochondria from rat brain: isolation and characterization J Neurochem 28 625–631 Occurrence Handle16086 Occurrence Handle1:CAS:528:DyaE2sXksl2kurg%3D Occurrence Handle10.1111/j.1471-4159.1977.tb10434.x

    Article  PubMed  CAS  Google Scholar 

  • OH Lowry NJ Rosebrough AL Farr RJ Randall (1951) ArticleTitleProtein measurement with the Folin phenol reagent J Biol Chem 193 265–275 Occurrence Handle14907713 Occurrence Handle1:CAS:528:DyaG38XhsVyrsw%3D%3D

    PubMed  CAS  Google Scholar 

  • M Martinez AI Hernandez N Martinez ML Ferrandiz (1996) ArticleTitleAge-related increase in oxidized proteins in mouse synaptic mitochondria Brain Res 731 246–248 Occurrence Handle8883880 Occurrence Handle1:CAS:528:DyaK28XkvFSrsLY%3D Occurrence Handle10.1016/0006-8993(96)00708-1

    Article  PubMed  CAS  Google Scholar 

  • JD Michenfelder JH Milde (1975) ArticleTitleInfluence of anesthetics on metabolic, functional and pathological response to regional cerebral ischemia Stroke 6 405–410 Occurrence Handle808000 Occurrence Handle1:CAS:528:DyaE2MXlt1Kgu70%3D

    PubMed  CAS  Google Scholar 

  • P Mullany S Conolly MA Lynch (1996) ArticleTitleAgeing is associated with changes in glutamate release, protein tyrosine kinase and Ca++/calmodulin-dependent protein kinase II in rat hippocampus Eur J Pharmacol 309 311–315 Occurrence Handle8874156 Occurrence Handle1:CAS:528:DyaK28XkvFWjsro%3D Occurrence Handle10.1016/0014-2999(96)00464-5

    Article  PubMed  CAS  Google Scholar 

  • A Nason FD Vasington (1963) Lipid dependent DPNH-cytochrome c reductase from mammalian skeletal and heart muscle SP Colowick NO Kaplan (Eds) Methods in Enzymology NumberInSeries6 Academic Press New York and London 409–415 Occurrence Handle10.1016/0076-6879(63)06197-8

    Chapter  Google Scholar 

  • L Nilsson BK Siesjö (1970) ArticleTitleThe effects of anesthetics upon labile phosphates and upon extra- and intra-cellular lactate, pyruvate and bicarbonate concentrations in the rat brain Acta Physiol Scand 80 235–248 Occurrence Handle5475343 Occurrence Handle1:CAS:528:DyaE3cXlt12htL8%3D Occurrence Handle10.1111/j.1748-1716.1970.tb04787.x

    Article  PubMed  CAS  Google Scholar 

  • L Nilsson BK Siesjö (1974) ArticleTitleInfluence of anesthetics on the balance between production and utilization of energy in the brain J Neurochem 23 29–36 Occurrence Handle4852427 Occurrence Handle1:CAS:528:DyaE2cXls1emsrw%3D Occurrence Handle10.1111/j.1471-4159.1974.tb06912.x

    Article  PubMed  CAS  Google Scholar 

  • S Ochoa (1955) Malic dehydrogenase from pig heart SP Colowick NO Kaplan (Eds) Methods in Enzymology NumberInSeries1 Academic Press New York and London 735–739 Occurrence Handle10.1016/0076-6879(55)01128-2

    Chapter  Google Scholar 

  • N Ragusa RF Villa G Magrì F Ingrao A Gorini L Turpeenoja AM Giuffrida-Stella (1992) ArticleTitleModifications of synaptosomal plasma membrane protein composition in various brain regions during aging Int J Dev Neuroscience 10 265–272 Occurrence Handle1:CAS:528:DyaK3sXksVGh Occurrence Handle10.1016/0736-5748(92)90015-R

    Article  CAS  Google Scholar 

  • J Sastre FV Pallardò J Vina (2000) ArticleTitleMitochondrial oxidative stress plays a key role in ageing and apoptosis Life 49 427–435 Occurrence Handle10902575 Occurrence Handle1:CAS:528:DC%2BD3cXks12htrk%3D

    PubMed  CAS  Google Scholar 

  • L Smith (1955) Spectrophotometric assay of cytochrome c oxidase D Glick (Eds) Methods of Biochemical Analysis NumberInSeries2 Wiley-Interscience New York 427–434

    Google Scholar 

  • AL Smith JT Hoff L Nielsen CP Larson (1974a) ArticleTitleBarbiturate protection in acute focal cerebral ischemia Stroke 5 1–7 Occurrence Handle1:CAS:528:DyaE2cXksVGgur4%3D

    CAS  Google Scholar 

  • L Smith HC Davies M Nava (1974b) ArticleTitleOxidation and reduction of soluble cytochrome c by membrane-bound oxidase and reductase system J Biol Chem 249 2904–2910 Occurrence Handle1:CAS:528:DyaE2cXksVKrt7Y%3D

    CAS  Google Scholar 

  • PH Sugden EA Newsholme (1975) ArticleTitleActivities of citrate synthase, NAD+-linked and NADP+-linked isocitrate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in nervous tissues from vertebrates and invertebrates Biochem J 150 105–111 Occurrence Handle1003 Occurrence Handle1:CAS:528:DyaE2MXlt1yqt7o%3D

    PubMed  CAS  Google Scholar 

  • L Turpeenoja RF Villa G Magrì AM Giuffrida-Stella (1988) ArticleTitleChanges of mitochondrial membrane proteins in rat cerebellum during ageing Neurochem Res 13 859–865 Occurrence Handle3226468 Occurrence Handle1:CAS:528:DyaL1cXmtVyrs7s%3D Occurrence Handle10.1007/BF00970754

    Article  PubMed  CAS  Google Scholar 

  • RF Villa A Gorini (1991a) ArticleTitleAction of L-acetylcarnitine on different cerebral mitochondrial populations from hippocampus and striatum during aging Neurochem Res 16 1125–1132 Occurrence Handle1:CAS:528:DyaK3MXmslSms7Y%3D Occurrence Handle10.1007/BF00966590

    Article  CAS  Google Scholar 

  • RF Villa A Gorini (1991b) ArticleTitleEnzyme mitochondrial systems during aging: pharmacological implications Neuro Chem (Life Sci Adv) 10 49–59

    Google Scholar 

  • RF Villa A Gorini (1997) ArticleTitlePharmacology of lazaroids and brain energy metabolism: a review Pharmacological Review 49 99–136 Occurrence Handle1:CAS:528:DyaK2sXisFWkt7Y%3D

    CAS  Google Scholar 

  • RF Villa F Marzatico G Benzi (1983) ArticleTitleChanges induced by ischemia on some cerebral enzymatic activities related to energy transduction and amino acids metabolism Neurochem Res 8 269–290 Occurrence Handle6856030 Occurrence Handle1:CAS:528:DyaL3sXhvFGqt70%3D Occurrence Handle10.1007/BF00963926

    Article  PubMed  CAS  Google Scholar 

  • RF Villa A Gorini D Geroldi A Lo Faro C Dell’Orbo (1989a) ArticleTitleEnzyme activities of selected mitochondria from hippocampus and striatum in aging Mech Ageing Dev 49 211–225 Occurrence Handle1:CAS:528:DyaL1MXlvFaisr0%3D Occurrence Handle10.1016/0047-6374(89)90072-9

    Article  CAS  Google Scholar 

  • RF Villa A Gorini A LoFaro C Dell’Orbo (1989b) ArticleTitleA critique on the preparation and enzymatic characterization of synaptic and nonsynaptic mitochondria from hippocampus Cell Mol Neurobiol 9 247–262 Occurrence Handle1:STN:280:DyaL1MzgsVSitA%3D%3D Occurrence Handle10.1007/BF00713032

    Article  CAS  Google Scholar 

  • RF Villa L Turpeenoja G Magrì A Gorini N Ragusa AM Giuffrida-Stella (1991a) ArticleTitleEffect of hypoxia on mitochondrial protein composition of cerebral cortex during aging Neurochem Res 16 821–826 Occurrence Handle1:CAS:528:DyaK3MXmtVGju78%3D Occurrence Handle10.1007/BF00965692

    Article  CAS  Google Scholar 

  • RF Villa B Ghigini R Arnaboldi D Geroldi A Gorini (1991b) ArticleTitleFactors involved in drug interference on enzyme activities of three mitochondrial populations from rat hippocampus Eur J Basic Appl Histochem 35 409–421 Occurrence Handle1:CAS:528:DyaK38XisVyhtr4%3D

    CAS  Google Scholar 

  • RF Villa R Arnaboldi B Ghigini A Gorini (1992) ArticleTitleMitochondrial factors involved in Parkinson’s disease by MPTP toxicity in Macaca fascicularis and drug effect Neurochem Res 17 1147–1154 Occurrence Handle1461362 Occurrence Handle1:CAS:528:DyaK3sXhs1Wmsw%3D%3D Occurrence Handle10.1007/BF00967293

    Article  PubMed  CAS  Google Scholar 

  • RF Villa F Ingrao G Magrì A Gorini S Reale A Costa N Ragusa R Avola AM Giuffrida-Stella (1993) ArticleTitleEffect of CDP-Choline treatment on mitochondrial and synaptosomal protein composition in different brain regions during aging Int J Dev Neuroscience 11 83–93 Occurrence Handle1:CAS:528:DyaK3sXksVKjsbY%3D Occurrence Handle10.1016/0736-5748(93)90037-E

    Article  CAS  Google Scholar 

  • RF Villa R Arnaboldi B Ghigini A Gorini (1994) ArticleTitleParkinson-like disease by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) toxicity in Macaca fascicularis: synaptosomal metabolism and action of dihydroergocriptine Neurochem Res 19 229–236 Occurrence Handle8177363 Occurrence Handle1:CAS:528:DyaK2cXhsFKhsrc%3D Occurrence Handle10.1007/BF00971569

    Article  PubMed  CAS  Google Scholar 

  • RF Villa A Gorini S Hoyer (2002) ArticleTitleATP-ases of synaptic plasma membranes from hippocampus after ischemia and recovery during ageing Neurochem Res 27 861–870 Occurrence Handle12396096 Occurrence Handle1:CAS:528:DC%2BD38Xnt1ahs7c%3D Occurrence Handle10.1023/A:1020381829107

    Article  PubMed  CAS  Google Scholar 

  • DC Wharton A Tzagoloff (1967) Cytochrome oxidase from beef heart mitochondria RW Estabrook ME Pullman (Eds) Methods in Enzymology NumberInSeries10 Academic Press New York and London 245–250

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Villa, R., Gorini, A. & Hoyer, S. Differentiated effect of ageing on the enzymes of Krebs’ cycle, electron transfer complexes and glutamate metabolism of non-synaptic and intra-synaptic mitochondria from cerebral cortex. J Neural Transm 113, 1659–1670 (2006). https://doi.org/10.1007/s00702-006-0569-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-006-0569-4

Navigation