Selegiline reverses aß25â35-induced cognitive deficit in male mice.
Neurochem Res
; 38(11): 2287-94, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-24005822
ABSTRACT
Alzheimer's disease (AD) is biochemically characterized by the occurrence of extracellular deposits of amyloid beta peptide (Aß) 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 Aß25-35 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 Aß25-35-injected male mice. Acute (1 and 10 mg/kg, p.o., immediately post-training) and subchronic (10 mg/kg, p.o., seven days after Aß25-35 injection and immediately post-training) administration of selegiline reversed the cognitive impairment induced by Aß25-35 (3 nmol, i.c.v.). Acute administration of selegiline (1 mg/kg, p.o.) in combination with Aß25-35 (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 Aß25-35 or Aß35-25 treatment. MAO-A activity was not altered by selegiline or Aß25-35. In summary, the current findings further support a role for cortical monoaminergic transmission in the cognitive deficits observed in AD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Selegilina
/
Transtornos Cognitivos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article