Ryanodine receptor-mediated interference of neuronal cell differentiation by presenilin 2 mutation

J Neurosci Res. 2005 Nov 15;82(4):542-50. doi: 10.1002/jnr.20655.

Abstract

Neuronal cell differentiation alterations induced by mutant presenilin 2 (PS2) were investigated in transgenic mice expressing wild-type or mutant-type PS2. Progressive increases in differentiation and marker protein expression were found in neuronal cells expressing wild-type PS2, whereas these processes were much perturbed in mutant-type PS2 with elevated ryanodine-receptor (RyR) expression and intracellular calcium levels. Moreover, dantrolene, a blocker of RyR reduced the PS2 mutation-induced interference of cell differentiation and calcium release, but caffeine, an activator of RyR, exacerbated PS2 mutation-induced interference with cell differentiation. Our results indicate that mutant PS2 inhibits normal neuronal cell differentiation and that RyR-mediated calcium overrelease may be a significant factor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western / methods
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Dantrolene / pharmacology
  • Drug Interactions
  • Embryo, Mammalian
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Gene Expression Regulation / genetics
  • Immunohistochemistry / methods
  • Intermediate Filament Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Transgenic
  • Mutation*
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neurofilament Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Phosphodiesterase Inhibitors / pharmacology
  • Presenilin-2
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Ryanodine Receptor Calcium Release Channel / physiology*
  • Time Factors

Substances

  • Intermediate Filament Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Neurofilament Proteins
  • Phosphodiesterase Inhibitors
  • Presenilin-2
  • RNA, Messenger
  • Ryanodine Receptor Calcium Release Channel
  • Caffeine
  • Dantrolene
  • Calcium