, Volume 38, Issue 11, pp 2287-2294
Date: 05 Sep 2013

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

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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.

Andréia M. Pazini and Guilherme M. Gomes have contributed equally to this work.