A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats.
Acta Pharmacol Sin
; 37(4): 444-52, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26838073
ABSTRACT
AIM:
A novel coumarin derivative 7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) has shown anti-apoptotic, anti-inflammatory and neuroprotective activities. In this study we investigated the effects of IMM-H004 on spatial memory in rats treated with okadaic acid (OKA), which was used to imitate Alzheimer's disease (AD)-like symptoms.METHODS:
SD rats were administered IMM-H004 (8 mg·kg(-1)·d(-1), ig) or donepezil (positive control, 1 mg·kg(-1)·d(-1), ig) for 25 d. On d 8 and 9, OKA (200 ng) was microinjected into the right ventricle. Morris water maze test was used to evaluate the spatial memory impairments. Tau and ß-amyloid (Aß) pathology in the hippocampus was detected using Western blot and immunohistochemistry. TUNEL staining was used to detect cell apoptosis.RESULTS:
OKA-treated rats showed significant impairments of spatial memory in Morris water maze test, which were largely reversed by administration of IMM-H004 or donepezil. Furthermore, OKA-treated rats exhibited significantly increased phosphorylation of tau, deposits of Aß protein and cell apoptosis in the hippocampus, which were also reversed by administration of IMM-H004 or donepezil.CONCLUSION:
Administration of IMM-H004 or donepezil protects rats against OKA-induced spatial memory impairments via attenuating tau or Aß pathology. Thus, IMM-H004 may be developed as a therapeutic agent for the treatment of AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cumarínicos
/
Memória Espacial
/
Transtornos da Memória
Limite:
Animals
Idioma:
En
Revista:
Acta Pharmacol Sin
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China