AGE

, Volume 35, Issue 5, pp 1589–1606

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

DOI: 10.1007/s11357-012-9462-2

Cite this article as:
Marquet-de Rougé, P., Clamagirand, C., Facchinetti, P. et al. AGE (2013) 35: 1589. doi:10.1007/s11357-012-9462-2

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

AgingAmyloid precursor proteinBrainCholesterolLipid raftsCaveolin-1Citrulline dietHippocampusRodent

Supplementary material

11357_2012_9462_Fig8_ESM.jpg (38 kb)
Fig. 1S

Detection of hippocampal rodent raft subpopulations. (A) Representative immunoblots showing the co-detection of F3 and Flotillin-1 in YNG, NEAA, and CIT rats. A 12–30 % continuous sucrose gradient was used. Similar patterns were obtained for the two proteins. (B) Representative co-detection of GM1 (dot blots) and FLOT-1 in mouse rafts. A 5–30 % continuous sucrose gradient was used. GM1 and FLOT-1 presented similar patterns. These three raft-specific markers displayed maximal levels of expression in the same fractions (JPEG 38 kb)

11357_2012_9462_MOESM1_ESM.tif (4.3 mb)
High resolution image (TIFF 4355 kb)
11357_2012_9462_Fig9_ESM.jpg (42 kb)
Fig. 1S

Detection of hippocampal rodent raft subpopulations. (A) Representative immunoblots showing the co-detection of F3 and Flotillin-1 in YNG, NEAA, and CIT rats. A 12–30 % continuous sucrose gradient was used. Similar patterns were obtained for the two proteins. (B) Representative co-detection of GM1 (dot blots) and FLOT-1 in mouse rafts. A 5–30 % continuous sucrose gradient was used. GM1 and FLOT-1 presented similar patterns. These three raft-specific markers displayed maximal levels of expression in the same fractions (JPEG 38 kb)

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

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