FLZ, synthetic squamosamide cyclic derivative, attenuates memory deficit and pathological changes in mice with experimentally induced aging.

Abstract

The aim of this study was to investigate the protective effects of N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide (FLZ), a synthetic squamosamide cyclic derivative, on senescent mice induced by D: -galactose/NaNO(2) (120/90 mg/kg, i.p.) once daily for 60 days. FLZ (75 and 150 mg/kg) was orally administered once daily for 30 days after D: -galactose/NaNO(2) treatment for 30 days. The cognitive function of mice was evaluated with step-down task. The brain biomarkers including monoamine oxidase B (MAO-B), glutathione peroxidase (GSH-px), and malondialdehyde (MDA) were determined according to the manufacturer's instructions. The expression of acetylcholinesterase (ACh-E) and choline acetyltransferase (ChAT) protein in the CA1 region of hippocampus were counted by immunohistochemical staining. The results showed that the cognitive function, GSH-px activity in the brain, and the expression of ACh-E and ChAT in the CA1 region of hippocampus were significantly decreased, while MAO-B activity and MDA level in the brain were increased in senescent mice compared with the control mice. FLZ treatment prolonged the step-down latency and decreased the number of step-down errors in the senescent mice. In addition, FLZ treatment increased the GSH-px activity and the expression of ACh-E and ChAT in the hippocampus and decreased the MDA level and MAO-B activity compared with the senescent mice without drug administration. These findings suggested that FLZ improves the performance in the step-down task and the pathological alternations in senescent mice.

• Authors: Fang Fang, Qing-li Wang, Geng-tao Liu
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 385 Issue 6 Pg. 579-85 (Jun 2012) ISSN: 1432-1912 [Electronic] Germany
• PMID: 22447151 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzeneacetamides
• Neuroprotective Agents
• Phenols
• squamosamide
• Malondialdehyde
• Glutathione Peroxidase
• Monoamine Oxidase
• Sodium Nitrite
• Galactose

Topics

• Aging (physiology)
• Animals
• Avoidance Learning (drug effects)
• Benzeneacetamides (pharmacology, therapeutic use)
• Brain (drug effects, pathology, physiopathology)
• Disease Models, Animal
• Galactose
• Glutathione Peroxidase (metabolism)
• Male
• Malondialdehyde (metabolism)
• Memory Disorders (chemically induced, drug therapy, physiopathology)
• Mice
• Mice, Inbred ICR
• Monoamine Oxidase (metabolism)
• Neurons (drug effects, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Phenols (pharmacology, therapeutic use)
• Sodium Nitrite