DMXB (GTS-21) ameliorates the cognitive deficits in beta amyloid(25-35(-) ) injected mice through preventing the dysfunction of alpha7 nicotinic receptor

J Neurosci Res. 2010 Jun;88(8):1784-94. doi: 10.1002/jnr.22345.


Intracerebroventricular injection of beta-amyloid(25-35) (Abeta(25-35)) in mice leads to cognitive deficits with the dysfunction of alpha7 nicotinic acetylcholine receptor (alpha7nAChR) within 1-2 weeks in a dose-dependent manner. The present study focused on the effect of DMXB, a selective alpha7nAChR agonist, on Abeta(25-35) (3 nmol)-impaired spatial memory and alpha7nAChR function. We found that the treatment with DMXB on days 1-10 after Abeta(25-35) injection dose-dependently prevented Abeta(25-35)-induced impairment of acquisition performance and probe trail test in Morris water maze. Importantly, the treatment with DMXB (1 mg/kg) perfectly prevented Abeta(25-35)-induced depression of alpha7nAChR response, which was associated with improving the probability of presynaptic glutamate release and the induction of high-frequency stimulation (HFS)-dependent long-term potentiation (LTP) in hippocampal Schaffer collaterale-CA1 synapse. Furthermore, although either the basal level of extracellular signal-regulated kinase 2 (ERK2) or its phosphorylation in the hippocampus had no difference between control and Abeta(25-35) mice, the Abeta(25-35) injection significantly attenuated HFS-triggered increase in ERK2 phosphorylation. The treatment with DMXB also rescued the ERK2 phosphorylation triggered by HFS in Abeta(25-35) mice that is required for LTP induction. This study firstly provides in vivo evidence that the anti-amnesic effect of DMXB is likely due to preventing the Abeta(25-35)-induced dysfunction of alpha7nAChR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides*
  • Animals
  • Behavior, Animal / drug effects
  • Benzylidene Compounds / therapeutic use*
  • Cognition Disorders / chemically induced
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electric Stimulation / methods
  • Evoked Potentials / drug effects
  • Gene Expression Regulation / drug effects
  • Hippocampus / drug effects
  • Hippocampus / physiopathology
  • In Vitro Techniques
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred ICR
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Neuronal Plasticity / drug effects
  • Nicotinic Agonists / therapeutic use*
  • Peptide Fragments*
  • Phosphorylation / drug effects
  • Pyridines / therapeutic use*
  • Reaction Time / drug effects
  • Receptors, Nicotinic / metabolism*
  • Space Perception / drug effects
  • alpha7 Nicotinic Acetylcholine Receptor


  • Amyloid beta-Peptides
  • Benzylidene Compounds
  • Chrna7 protein, mouse
  • Nicotinic Agonists
  • Peptide Fragments
  • Pyridines
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • amyloid beta-protein (25-35)
  • 3-(2,4-dimethoxybenzylidene)anabaseine
  • Mitogen-Activated Protein Kinase 1