AGE

, Volume 35, Issue 5, pp 1589–1606 | Cite as

Citrulline diet supplementation improves specific age-related raft changes in wild-type rodent hippocampus

  • Perrine Marquet-de Rougé
  • Christine Clamagirand
  • Patricia Facchinetti
  • Christiane Rose
  • Françoise Sargueil
  • Chantal Guihenneuc-Jouyaux
  • Luc Cynober
  • Christophe Moinard
  • Bernadette Allinquant
Article

Abstract

The levels of molecules crucial for signal transduction processing change in the brain with aging. Lipid rafts are membrane microdomains involved in cell signaling. We describe here substantial biophysical and biochemical changes occurring within the rafts in hippocampus neurons from aging wild-type rats and mice. Using continuous sucrose density gradients, we observed light-, medium-, and heavy raft subpopulations in young adult rodent hippocampus neurons containing very low levels of amyloid precursor protein (APP) and almost no caveolin-1 (CAV-1). By contrast, old rodents had a homogeneous age-specific high-density caveolar raft subpopulation containing significantly more cholesterol (CHOL), CAV-1, and APP. C99-APP-Cter fragment detection demonstrates that the first step of amyloidogenic APP processing takes place in this caveolar structure during physiological aging of the rat brain. In this age-specific caveolar raft subpopulation, levels of the C99-APP-Cter fragment are exponentially correlated with those of APP, suggesting that high APP concentrations may be associated with a risk of large increases in beta-amyloid peptide levels. Citrulline (an intermediate amino acid of the urea cycle) supplementation in the diet of aged rats for 3 months reduced these age-related hippocampus raft changes, resulting in raft patterns tightly close to those in young animals: CHOL, CAV-1, and APP concentrations were significantly lower and the C99-APP-Cter fragment was less abundant in the heavy raft subpopulation than in controls. Thus, we report substantial changes in raft structures during the aging of rodent hippocampus and describe new and promising areas of investigation concerning the possible protective effect of citrulline on brain function during aging.

Keywords

Aging Amyloid precursor protein Brain Cholesterol Lipid rafts Caveolin-1 Citrulline diet Hippocampus Rodent 

Notes

Acknowledgments

This work was supported by INSERM (ATC Vieillissement 2002), Université Paris Descartes (ATP aging). We thank Dr. Kenneth L. Moya for his helpful comments and his expert editing of the manuscript. We are grateful to Servane Le Plenier for her help with animal care.

Supplementary material

11357_2012_9462_MOESM1_ESM.tif (4.3 mb)
High resolution image (TIFF 4355 kb)
11357_2012_9462_MOESM2_ESM.tif (1.5 mb)
High resolution image (TIFF 1525 kb)

References

  1. Bickel PE, Scherer PE, Schnitzer JE, Oh P, Lisanti MP, Lodish HF (1997) Flotillin and epidermal surface antigen define a new family of caveolae-associated integral membrane proteins. J Biol Chem 272:13793–13802PubMedCrossRefGoogle Scholar
  2. Bohme GA, Bon C, Lemaire M, Reibaud M, Piot O, Stutzmann JM, Doble A, Blanchard JC (1993) Altered synaptic plasticity and memory formation in nitric oxide synthase inhibitor-treated rats. Proc Natl Acad Sci U S A 90:9191–9194PubMedCrossRefGoogle Scholar
  3. Bouillot C, Prochiantz A, Rougon G, Allinquant B (1996) Axonal amyloid precursor protein expressed by neurons in vitro is present in a membrane fraction with caveolae-like properties. J Biol Chem 271:7640–7644PubMedCrossRefGoogle Scholar
  4. Brouillet E, Trembleau A, Galanaud D, Volovitch M, Bouillot C, Valenza C, Prochiantz A, Allinquant B (1999) The amyloid precursor protein interacts with Go heterotrimeric protein within a cell compartment specialized in signal transduction. J Neurosci 19:1717–1727PubMedGoogle Scholar
  5. Chen TY, Liu PH, Ruan CT, Chiu L, Kung FL (2006) The intracellular domain of amyloid precursor protein interacts with flotillin-1, a lipid raft protein. Biochem Biophys Res Commun 342:266–272PubMedCrossRefGoogle Scholar
  6. Cho KA, Ryu SJ, Park JS, Jang IS, Ahn JS, Kim KT, Park SC (2003) Senescent phenotype can be reversed by reduction of caveolin status. J Biol Chem 278:27789–27795PubMedCrossRefGoogle Scholar
  7. Clement AB, Gamerdinger M, Tamboli IY, Lutjohann D, Walter J, Greeve I, Gimpl G, Behl C (2009) Adaptation of neuronal cells to chronic oxidative stress is associated with altered cholesterol and sphingolipid homeostasis and lysosomal function. J Neurochem 111:669–682PubMedCrossRefGoogle Scholar
  8. Clement AB, Gimpl G, Behl C (2010) Oxidative stress resistance in hippocampal cells is associated with altered membrane fluidity and enhanced nonamyloidogenic cleavage of endogenous amyloid precursor protein. Free Radic Biol Med 48:1236–1241PubMedCrossRefGoogle Scholar
  9. Congdon P (2006) Bayesian statistical modelling (2nd edition). Chapters 1 and 4: Chichester: Wiley, collection: Wiley series in probability and statisticsGoogle Scholar
  10. Cynober L, Moinard C, De Bandt JP (2010) The 2009 ESPEN Sir David Cuthbertson. Citrulline: a new major signaling molecule or just another player in the pharmaconutrition game? Clin Nutr 29:545–551PubMedCrossRefGoogle Scholar
  11. Ehehalt R, Keller P, Haass C, Thiele C, Simons K (2003) Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J Cell Biol 160:113–123PubMedCrossRefGoogle Scholar
  12. Gaudreault SB, Dea D, Poirier J (2004) Increased caveolin-1 expression in Alzheimer’s disease brain. Neurobiol Aging 25:753–759PubMedCrossRefGoogle Scholar
  13. Gelman A, Carlin JB, Stern HS, Rubin B (2004) Bayesian data analysis. Chapter 4, 2nd edn. Chapman & Hall/CRC, Boca Raton, collection: texts in statistical scienceGoogle Scholar
  14. Gylys KH, Fein JA, Yang F, Miller CA, Cole GM (2007) Increased cholesterol in Abeta-positive nerve terminals from Alzheimer’s disease cortex. Neurobiol Aging 28:8–17PubMedCrossRefGoogle Scholar
  15. Head BP, Peart JN, Panneerselvam M, Yokoyama T, Pearn ML, Niesman IR, Bonds JA, Schilling JM, Miyanohara A, Headrick J, Ali SS, Roth DM, Patel PM, Patel HH (2010) Loss of caveolin-1 accelerates neurodegeneration and aging. PLoS One 5:e15697PubMedCrossRefGoogle Scholar
  16. Heverin M, Bogdanovic N, Lutjohann D, Bayer T, Pikuleva I, Bretillon L, Diczfalusy U, Winblad B, Bjorkhem I (2004) Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer’s disease. J Lipid Res 45:186–193PubMedCrossRefGoogle Scholar
  17. Hudry E, Van Dam D, Kulik W, De Deyn PP, Stet FS, Ahouansou O, Benraiss A, Delacourte A, Bougneres P, Aubourg P, Cartier N (2010) Adeno-associated virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimer’s disease. Mol Ther 18:44–53PubMedCrossRefGoogle Scholar
  18. Igbavboa U, Avdulov NA, Schroeder F, Wood WG (1996) Increasing age alters transbilayer fluidity and cholesterol asymmetry in synaptic plasma membranes of mice. J Neurochem 66:1717–1725PubMedCrossRefGoogle Scholar
  19. Igbavboa U, Eckert GP, Malo TM, Studniski AE, Johnson LN, Yamamoto N, Kobayashi M, Fujita SC, Appel TR, Muller WE, Wood WG, Yanagisawa K (2005) Murine synaptosomal lipid raft protein and lipid composition are altered by expression of human apoE 3 and 4 and by increasing age. J Neurol Sci 229–230:225–232PubMedCrossRefGoogle Scholar
  20. Ikezu T, Trapp BD, Song KS, Schlegel A, Lisanti MP, Okamoto T (1998) Caveolae, plasma membrane microdomains for alpha-secretase-mediated processing of the amyloid precursor protein. J Biol Chem 273:10485–10495PubMedCrossRefGoogle Scholar
  21. Jiang L, Fang J, Moore DS, Gogichaeva NV, Galeva NA, Michaelis ML, Zaidi A (2010) Age-associated changes in synaptic lipid raft proteins revealed by two-dimensional fluorescence difference gel electrophoresis. Neurobiol Aging 31:2146–2159PubMedCrossRefGoogle Scholar
  22. Kang MJ, Chung YH, Hwang CI, Murata M, Fujimoto T, Mook-Jung IH, Cha CI, Park WY (2006) Caveolin-1 upregulation in senescent neurons alters amyloid precursor protein processing. Exp Mol Med 38:126–133PubMedCrossRefGoogle Scholar
  23. Kurzchalia TV, Parton RG (1999) Membrane microdomains and caveolae. Curr Opin Cell Biol 11:424–431PubMedCrossRefGoogle Scholar
  24. Langui D, Girardot N, El Hachimi KH, Allinquant B, Blanchard V, Pradier L, Duyckaerts C (2004) Subcellular topography of neuronal Abeta peptide in APPxPS1 transgenic mice. Am J Pathol 165:1465–1477PubMedCrossRefGoogle Scholar
  25. Larbi A, Douziech N, Dupuis G, Khalil A, Pelletier H, Guerard KP, Fulop T Jr (2004) Age-associated alterations in the recruitment of signal-transduction proteins to lipid rafts in human T lymphocytes. J Leukoc Biol 75:373–381PubMedCrossRefGoogle Scholar
  26. Law A, O’Donnell J, Gauthier S, Quirion R (2002) Neuronal and inducible nitric oxide synthase expressions and activities in the hippocampi and cortices of young adult, aged cognitively unimpaired, and impaired Long–Evans rats. Neuroscience 112:267–275PubMedCrossRefGoogle Scholar
  27. Le PU, Guay G, Altschuler Y, Nabi IR (2002) Caveolin-1 is a negative regulator of caveolae-mediated endocytosis to the endoplasmic reticulum. J Biol Chem 277:3371–3379PubMedCrossRefGoogle Scholar
  28. Lisanti MP, Scherer PE, Vidugiriene J, Tang Z, Hermanowski-Vosatka A, Tu YH, Cook RF, Sargiacomo M (1994) Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease. J Cell Biol 126:111–126PubMedCrossRefGoogle Scholar
  29. Marquer C, Devauges V, Cossec JC, Liot G, Lecart S, Saudou F, Duyckaerts C, Leveque-Fort S, Potier MC (2011) Local cholesterol increase triggers amyloid precursor protein-Bace1 clustering in lipid rafts and rapid endocytosis. FASEB J 25:1295–1305PubMedCrossRefGoogle Scholar
  30. Moinard C, Walrand S, Boirie Y, Cynober L (2007) Therapeutic use of Citrulline in treatment of increased protein carbonylation-associated diseases. Pattent number 07/02090 applied the 03/22/2007Google Scholar
  31. Murata M, Peranen J, Schreiner R, Wieland F, Kurzchalia TV, Simons K (1995) VIP21/caveolin is a cholesterol-binding protein. Proc Natl Acad Sci USA 92:10339–10343PubMedCrossRefGoogle Scholar
  32. Necchi D, Virgili M, Monti B, Contestabile A, Scherini E (2002) Regional alterations of the NO/NOS system in the aging brain: a biochemical, histochemical and immunochemical study in the rat. Brain Res 933:31–41PubMedCrossRefGoogle Scholar
  33. Nichols B (2003) Caveosomes and endocytosis of lipid rafts. J Cell Sci 116:4707–4714PubMedCrossRefGoogle Scholar
  34. Noda Y, Yamada K, Nabeshima T (1997) Role of nitric oxide in the effect of aging on spatial memory in rats. Behav Brain Res 83:153–158PubMedCrossRefGoogle Scholar
  35. Oda A, Tamaoka A, Araki W (2010) Oxidative stress up-regulates presenilin 1 in lipid rafts in neuronal cells. J Neurosci Res 88:1137–1145PubMedGoogle Scholar
  36. Park WY, Park JS, Cho KA, Kim DI, Ko YG, Seo JS, Park SC (2000) Up-regulation of caveolin attenuates epidermal growth factor signaling in senescent cells. J Biol Chem 275:20847–20852PubMedCrossRefGoogle Scholar
  37. Paul V, Ekambaram P (2011) Involvement of nitric oxide in learning & memory processes. Indian J Med Res 133:471–478PubMedGoogle Scholar
  38. Pike LJ (2004) Lipid rafts: heterogeneity on the high seas. Biochem J 378:281–292PubMedCrossRefGoogle Scholar
  39. Refolo LM, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Tint GS, Sambamurti K, Duff K, Pappolla MA (2000) Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model. Neurobiol Dis 7:321–331PubMedCrossRefGoogle Scholar
  40. Robert CP (2001) The Bayesian choice: from decision-theoretic motivations to computational implementation. Chapters 3 and 11. Springer, New-YorkGoogle Scholar
  41. Russell DW, Halford RW, Ramirez DM, Shah R, Kotti T (2009) Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain. Annu Rev Biochem 78:1017–1040PubMedCrossRefGoogle Scholar
  42. Sargiacomo M, Sudol M, Tang Z, Lisanti MP (1993) Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. J Cell Biol 122:789–807PubMedCrossRefGoogle Scholar
  43. Sato Y, Sagami I, Shimizu T (2004) Identification of caveolin-1-interacting sites in neuronal nitric-oxide synthase. Molecular mechanism for inhibition of NO formation. J Biol Chem 279:8827–8836PubMedCrossRefGoogle Scholar
  44. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572PubMedCrossRefGoogle Scholar
  45. Simons M, Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K (1998) Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc Natl Acad Sci USA 95:6460–6464PubMedCrossRefGoogle Scholar
  46. Song KS, Li S, Okamoto T, Quilliam LA, Sargiacomo M, Lisanti MP (1996) Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. Detergent-free purification of caveolae microdomains. J Biol Chem 271:9690–9697PubMedCrossRefGoogle Scholar
  47. Spiegelhalter DJ, Best NG, Carlin BR, van der Linde A (2002) Bayesian measures of model complexity and fit. J Roy Stat Soc Ser B: 583-616Google Scholar
  48. Vetrivel KS, Thinakaran G (2010) Membrane rafts in Alzheimer’s disease beta-amyloid production. Biochim Biophys Acta 1801:860–867PubMedCrossRefGoogle Scholar
  49. Wahrle S, Das P, Nyborg AC, McLendon C, Shoji M, Kawarabayashi T, Younkin LH, Younkin SG, Golde TE (2002) Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane microdomains. Neurobiol Dis 9:11–23PubMedCrossRefGoogle Scholar
  50. Yaqoob P (2009) The nutritional significance of lipid rafts. Annu Rev Nutr 29:257–282PubMedCrossRefGoogle Scholar
  51. Yeo EJ, Park SC (2002) Age-dependent agonist-specific dysregulation of membrane-mediated signal transduction: emergence of the gate theory of aging. Mech Ageing Dev 123:1563–1578PubMedCrossRefGoogle Scholar
  52. Yokota A, Kawasaki S, Iwano M, Nakamura C, Miyake C, Akashi K (2002) Citrulline and DRIP-1 protein (ArgE homologue) in drought tolerance of wild watermelon. Ann Bot 89 Spec No: 825-832Google Scholar

Copyright information

© American Aging Association 2012

Authors and Affiliations

  • Perrine Marquet-de Rougé
    • 2
  • Christine Clamagirand
    • 1
  • Patricia Facchinetti
    • 1
  • Christiane Rose
    • 1
  • Françoise Sargueil
    • 3
  • Chantal Guihenneuc-Jouyaux
    • 4
  • Luc Cynober
    • 2
    • 5
  • Christophe Moinard
    • 2
  • Bernadette Allinquant
    • 1
  1. 1.INSERM UMR 894, Université Paris DescartesSorbonne Paris Cité, Faculté de MédecineParisFrance
  2. 2.EA 4466, Université Paris DescartesSorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et BiologiquesParisFrance
  3. 3.CNRS UMR 5544 and Université Bordeaux 2BordeauxFrance
  4. 4.EA 4064, Université Paris DescartesSorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et BiologiquesParisFrance
  5. 5.Service de Biochimie Hôtel-Dieu et CochinAP-HPParisFrance

Personalised recommendations