A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats.

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 β-amyloid (Aβ) 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 Aβ 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 Aβ pathology. Thus, IMM-H004 may be developed as a therapeutic agent for the treatment of AD.

• Authors: Xiu-yun Song, Ying-ying Wang, Shi-feng Chu, Jin-feng Hu, Peng-fei Yang, Wei Zuo, Lian-kun Song, Shuai Zhang, Nai-hong Chen
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 37 Issue 4 Pg. 444-52 (Apr 2016) ISSN: 1745-7254 [Electronic] United States
• PMID: 26838073 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Coumarins
• IMM-H004
• tau Proteins
• Okadaic Acid

Topics

• Amyloid beta-Peptides (metabolism)
• Animals
• Coumarins (administration & dosage, therapeutic use)
• Male
• Memory Disorders (chemically induced, drug therapy)
• Okadaic Acid
• Rats, Sprague-Dawley
• Spatial Memory (drug effects)
• tau Proteins (metabolism)