The galanin receptor 2/3 agonist Gal2-11 protects the SN56 cells against beta-amyloid 25-35 toxicity

J Neurosci Res. 2010 Apr;88(5):1064-73. doi: 10.1002/jnr.22278.

Abstract

The neuropeptide galanin is a modulator of cholinergic function and may play a role in A beta peptide-induced degeneration of cholinergic forebrain neurons. We have studied the effect of galanin and its galanin receptor subtype 2/3 agonist Gal2-11on toxicity induced by freshly-prepared beta-amyloid(25-35) in the cholinergic cell line SN56. Both nuclear fragmentation and caspase-3 expression were analysed. beta-amyloid(25-35)-exposure induced a significant increase in caspase-3 mRNA expression after 30, 60, 90 or 150 min of beta-amyloid(25-35) exposure. These effects were abolished in the presence of Gal2-11 (10 nM). Similarly, beta-amyloid(25-35)-induced nuclear fragmentation was prevented by the galanin agonist at all time points studied. These findings indicate that the galanin 2/3 agonist Gal2-11 protects SN56 cholinergic cells from beta-amyloid(25-35)-induced cell death and that this action is mediated by an early reduction of caspase-3 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Basal Nucleus of Meynert / drug effects
  • Basal Nucleus of Meynert / metabolism
  • Basal Nucleus of Meynert / physiopathology
  • Caspase 3 / genetics
  • Cell Line, Transformed
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / metabolism
  • Cholinergic Fibers / pathology
  • DNA Fragmentation / drug effects
  • Galanin / metabolism
  • Galanin / pharmacology*
  • Galanin / therapeutic use
  • Mice
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / therapeutic use
  • Peptide Fragments / toxicity
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Receptor, Galanin, Type 2 / agonists*
  • Receptor, Galanin, Type 2 / metabolism
  • Time Factors

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Peptide Fragments
  • RNA, Messenger
  • Receptor, Galanin, Type 2
  • amyloid beta-protein (25-35)
  • galanin (2-11)-amide
  • Galanin
  • Caspase 3
  • Acetylcholine