Beneficial effects of a neurotrophic peptidergic mixture persist for a prolonged period following treatment interruption in a transgenic model of Alzheimer's disease

J Neurosci Res. 2011 Nov;89(11):1812-21. doi: 10.1002/jnr.22712. Epub 2011 Jul 25.

Abstract

Neurodegenerative disorders such as Alzheimer's disease (AD) are characterized by the loss of neurotrophic factors, and experimental therapeutical approaches to AD have investigated the efficacy of replacing or augmenting neurotrophic factor activity. Cerebrolysin, a peptide mixture with neurotrophic-like effects, has been shown to improve cognition in patients with AD and to reduce synaptic and behavioral deficits in transgenic (tg) mice overexpressing the amyloid precursor protein (APP). However, it is unclear how long-lasting the beneficial effects of Cerebrolysin are and whether or not behavioral and neuropathological alterations will reappear following treatment interruption. The objective of the present study was to investigate the consequences of interrupting Cerebrolysin treatment (washout effect) 3 and 6 months after the completion of a 3-month treatment period in APP tg mice. We demonstrate that, in APP tg mice, Cerebrolysin-induced amelioration of memory deficits in the water maze and reduction of neurodegenerative pathology persist for 3 months after treatment interruption; however, these effects dissipate 6 months following treatment termination. Immunohistochemical analysis demonstrated that the decrease in neocortical and hippocampal amyloid plaque load observed in Cerebrolysin-treated APP tg mice immediately after treatment was no longer apparent at 3 months after treatment interruption, indicating that the beneficial effects of Cerebrolysin at this time point were independent of its effect on amyloid-β deposition. In conclusion, the results demonstrate that the effects of Cerebrolysin persist for a significant period of time following treatment termination and suggest that this prolonged effect may involve the neurotrophic factor-like activity of Cerebrolysin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amino Acids / pharmacology
  • Amino Acids / therapeutic use*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Cognition Disorders / drug therapy
  • Cognition Disorders / pathology
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Maze Learning / drug effects*
  • Memory / drug effects*
  • Mice
  • Mice, Transgenic
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / pathology
  • Neurons / drug effects
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Nootropic Agents / pharmacology
  • Nootropic Agents / therapeutic use*

Substances

  • Amino Acids
  • Amyloid beta-Protein Precursor
  • Neuroprotective Agents
  • Nootropic Agents
  • cerebrolysin