alpha-Tocopherol affects neuronal plasticity in adult rat dentate gyrus: the possible role of PKCdelta

J Neurobiol. 2006 Jul;66(8):793-810. doi: 10.1002/neu.20255.

Abstract

Hippocampus dentate gyrus (DG) is characterized by neuronal plasticity processes in adulthood, and polysialylation of NCAM promotes neuronal plasticity. In previous investigations we found that alpha-tocopherol increased the PSA-NCAM-positive granule cell number in adult rat DG, suggesting that alpha-tocopherol may enhance neuronal plasticity. To verify this hypothesis, in the present study, structural remodeling in adult rat DG was investigated under alpha-tocopherol supplementation conditions. PSA-NCAM expression was evaluated by Western blotting, evaluation of PSA-NCAM-positive granule cell density, and morphometric analysis of PSA-NCAM-positive processes. In addition, the optical density of synaptophysin immunoreactivity and the synaptic profile density, examined by electron microscopy, were evaluated. Moreover, considering that PSA-NCAM expression has been found to be related to PKCdelta activity and alpha-tocopherol has been shown to inhibit PKC activity in vitro, Western blotting and immunohistochemistry followed by densitometry were used to analyze PKC. Our results demonstrated that an increase in PSA-NCAM expression and optical density of DG molecular layer synaptophysin immunoreactivity occurred in alpha-tocopherol-treated rats. Electron microscopy analysis showed that the increase in synaptophysin expression was related to an increase in synaptic profile density. In addition, Western blotting revealed a decrease in phospho-PKC Pan and phospho-PKCdelta, demonstrating that alpha-tocopherol is also able to inhibit PKC activity in vivo. Likewise, immunoreactivity for the active form of PKCdelta was lower in alpha-tocopherol-treated rats than in controls, while no changes were found in PKCdelta expression. These results demonstrate that alpha-tocopherol is an exogenous factor affecting neuronal plasticity in adult rat DG, possibly through PKCdelta inhibition.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Dendrites / metabolism
  • Dendrites / ultrastructure
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / enzymology
  • Dentate Gyrus / ultrastructure
  • Enzyme Inhibitors / pharmacology
  • Immunohistochemistry
  • Male
  • Microscopy, Electron, Transmission
  • Neural Cell Adhesion Molecule L1 / drug effects
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Presynaptic Terminals / drug effects*
  • Presynaptic Terminals / enzymology
  • Presynaptic Terminals / ultrastructure
  • Protein Kinase C-delta / antagonists & inhibitors*
  • Protein Kinase C-delta / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sialic Acids / metabolism
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / enzymology
  • Synaptic Membranes / ultrastructure
  • Synaptophysin / drug effects
  • Synaptophysin / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • alpha-Tocopherol / pharmacology*

Substances

  • Antioxidants
  • Enzyme Inhibitors
  • Neural Cell Adhesion Molecule L1
  • Sialic Acids
  • Synaptophysin
  • polysialyl neural cell adhesion molecule
  • Protein Kinase C-delta
  • alpha-Tocopherol