Abeta peptides as one of the crucial volume transmission signals in the trophic units and their interactions with homocysteine. Physiological implications and relevance for Alzheimer's disease

J Neural Transm (Vienna). 2007 Jan;114(1):21-31. doi: 10.1007/s00702-006-0564-9. Epub 2006 Sep 14.

Abstract

Amyloid peptides (Abeta) can operate as volume transmission (VT) signals since they are continuously released from cells of the central nervous system and diffuse in the extra-cellular space of the brain. They have both regulatory and trophic functions on cellular networks. In agreement with Abeta regulatory actions on glial-neuronal networks, the present paper reports new findings demonstrating that intrastriatal injections of Abeta peptides reduce striatal tyrosine hydroxylase, increase striatal GFAP immunoreactivities and lower pain threshold in experimental rats. Furthermore, it has been demonstrated that exogenous homocysteine (Hcy) binds Abeta(1-40) favouring its beta-sheet conformation both in vitro and in vivo and hence the formation of beta-fibrils and development of neurotoxicity. Thus, the hypothesis is discussed that Abeta peptides represent crucial VT-signals in the brain and their action is altered by dysmetabolic signals such as high Hcy extra-cellular levels, known to be an important risk factor for Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Brain / metabolism*
  • Brain / physiopathology
  • Cell Communication / physiology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Extracellular Space / physiology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Homocysteine / metabolism*
  • Homocysteine / toxicity
  • Male
  • Nerve Net / metabolism*
  • Nerve Net / physiopathology
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Peptide Fragments / metabolism
  • Peptide Fragments / toxicity
  • Plaque, Amyloid / metabolism
  • Protein Structure, Secondary / drug effects
  • Protein Structure, Secondary / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Amyloid beta-Peptides
  • Glial Fibrillary Acidic Protein
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • Homocysteine
  • Tyrosine 3-Monooxygenase