Neurochemical Research

, Volume 38, Issue 11, pp 2287–2294

Selegiline Reverses Aβ25–35-Induced Cognitive Deficit in Male Mice

  • Andréia M. Pazini
  • Guilherme M. Gomes
  • Jardel G. Villarinho
  • Claudio da Cunha
  • Francielle Pinheiro
  • Ana P. O. Ferreira
  • Carlos F. Mello
  • Juliano Ferreira
  • Maribel A. Rubin
Original Paper

DOI: 10.1007/s11064-013-1137-6

Cite this article as:
Pazini, A.M., Gomes, G.M., Villarinho, J.G. et al. Neurochem Res (2013) 38: 2287. doi:10.1007/s11064-013-1137-6

Abstract

Alzheimer’s disease (AD) is biochemically characterized by the occurrence of extracellular deposits of amyloid beta peptide (Aβ) and intracellular deposits of the hyperphosphorylated tau protein, which are causally related to the pathological hallmarks senile plaques and neurofibrillary tangles. Monoamine oxidase B (MAO-B) activity, involved in the oxidation of biogenic monoamines, is particularly high around the senile plaques and increased in AD patients in middle to late clinical stages of the disease. Selegiline is a selective and irreversible MAO-B inhibitor and, although clinical trials already shown the beneficial effect of selegiline on cognition of AD patients, its mechanism of action remains to be elucidated. Therefore, we first investigated whether selegiline reverses the impairment of object recognition memory induced by Aβ25–35 in mice, an established model of AD. In addition, we investigated whether selegiline alters MAO-B and MAO-A activities in the hippocampus, perirhinal and remaining cerebral cortices of Aβ25–35-injected male mice. Acute (1 and 10 mg/kg, p.o., immediately post-training) and subchronic (10 mg/kg, p.o., seven days after Aβ25–35 injection and immediately post-training) administration of selegiline reversed the cognitive impairment induced by Aβ25–35 (3 nmol, i.c.v.). Acute administration of selegiline (1 mg/kg, p.o.) in combination with Aβ25–35 (3 nmol) decreased MAO-B activity in the perirhinal and remaining cerebral cortices. Acute administration of selegiline (10 mg/kg, p.o.) decreased MAO-B activity in hippocampus, perirhinal and remaining cerebral cortices, regardless of Aβ25–35 or Aβ35–25 treatment. MAO-A activity was not altered by selegiline or Aβ25–35. In summary, the current findings further support a role for cortical monoaminergic transmission in the cognitive deficits observed in AD.

Keywords

Alzheimer’s disease MAO inhibitors MAO-B Perirhinal cortex Memory Object recognition 

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Andréia M. Pazini
    • 1
  • Guilherme M. Gomes
    • 2
  • Jardel G. Villarinho
    • 1
  • Claudio da Cunha
    • 3
  • Francielle Pinheiro
    • 1
  • Ana P. O. Ferreira
    • 2
  • Carlos F. Mello
    • 1
  • Juliano Ferreira
    • 1
    • 2
  • Maribel A. Rubin
    • 1
    • 2
  1. 1.Programa de Pós-graduação em Farmacologia, Centro de Ciências da SaúdeUniversidade Federal de Santa MariaSanta MariaBrazil
  2. 2.Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e ExatasUniversidade Federal de Santa MariaSanta MariaBrazil
  3. 3.Departamento de FarmacologiaUFPRCuritibaBrazil

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