Effect of alpha-7 nicotinic acetylcholine receptor activation on beta-amyloid induced recognition memory impairment. Possible role of neurovascular function

Acta Cir Bras. 2015 Nov;30(11):736-42. doi: 10.1590/S0102-865020150110000003.

Abstract

Purpose: To evaluate the effects of PHA-543613 (α7-nAChR agonist) and galantamine (acetylcholinesterase inhibitor (AChEI)) on recognition memory and neurovascular coupling (NVC) response in beta-amyloid (Aβ) 25-35-treated mice.

Methods: PHA-543613 (1 mg/kg, i.p.), and galantamine (3 mg/kg, s.c.), effects were tested in Aβ25-35 mice model of AD. α7-nAChR antagonist, methyllycaconitine (MLA) (1 mg/kg, i.p.), was used for evaluation of receptor blockade effects. Recognition memory in animals was assessed by the novel object recognition (NOR) task. NVC response was analyzed by laser-doppler flow meter in barrel cortex by whisker stimulation method.

Results: Both, PHA-543613 and galantamine improve recognition memory in Aβ-treated animals. However, the advantageous effects of PHA-543613 were significantly higher than galantamine. Also, pretreatment with MLA reversed both galantamine and PHA-543613 effects on NOR. Impaired NVC response in AD animals was improved by PHA-543613 and galantamine. However, MLA pretreatment disrupts this function.

Conclusion: Activation of α7-nAChR improved recognition memory possible through enhancement of neurovascular response in Alzheimer's disease in animals.

Publication types

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

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides*
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Cholinesterase Inhibitors / pharmacology*
  • Disease Models, Animal
  • Galantamine / pharmacology*
  • Laser-Doppler Flowmetry
  • Male
  • Memory Disorders / drug therapy*
  • Memory Disorders / physiopathology
  • Mice, Inbred BALB C
  • Neuropsychological Tests
  • Neurovascular Coupling / drug effects*
  • Neurovascular Coupling / physiology
  • Peptide Fragments*
  • Quinuclidines / pharmacology*
  • Recognition, Psychology / drug effects
  • Reproducibility of Results
  • Time Factors
  • Treatment Outcome
  • alpha7 Nicotinic Acetylcholine Receptor / metabolism*

Substances

  • Amyloid beta-Peptides
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cholinesterase Inhibitors
  • N-(1-azabicyclo(2.2.2)oct-3-yl)furo(2,3-c)pyridine-5-carboxamide
  • Peptide Fragments
  • Quinuclidines
  • alpha7 Nicotinic Acetylcholine Receptor
  • amyloid beta-protein (25-35)
  • Galantamine