We previously reported the protective effects of long-term administration of ferulic acid against the in vivo toxicity of β-amyloid peptide administered intracerebroventricularly in mice. In the present study, we investigated the effects of ferulic acid in transgenic amyloid precursor protein (APP)swe/presenilin 1 (PS1)dE9 (APP/PS1) mouse model of Alzheimer disease (AD). Chronic (for 6 months from the age of 6 to 12 months) oral administration of ferulic acid at a dose of 5.3 mg/kg/day significantly enhanced the performance in novel-object recognition task, and reduced amyloid deposition and interleukin-1 beta (IL-1β) levels in the frontal cortex. These results suggest that ferulic acid at a certain dosage could be useful for prevention and treatment of AD.Key words β-amyloid peptide; Alzheimer disease; amyloid precursor protein; presenilin 1; ferulic acid Abnormal accumulation of β-amyloid peptide (Aβ) in the brain is regarded to be important in the pathogenesis of Alzheimer disease (AD), a progressive neurodegenerative disorder.1,2) Thus, continuing efforts have been made to develop strategies targeting Aβ for prevention and treatment of AD. activities. We previously reported that long-term (4 weeks) administration of ferulic acid protects against intracerebroventricularly (i.c.v.) administered Aβ1→42-induced learning and memory impairment 8) and astrocyte and microglial activation [8][9][10] in mice. Furthermore, ferulic acid ethyl ester was reported to protect against Aβ1→42-induced oxidative stress both in vitro 11) and in vivo. 12) Ferulic acid was also reported to destabilize preformed Aβ fibrils in vitro.
13)In addition to the i.c.v. injection of Aβ1→42, 8) amyloid precursor protein (APP) transgenic 14) or APP/presenilin 1 (PS1) double transgenic 15) mice have been very useful for evaluation of beneficial effects of substances targeting Aβ in vivo. Thus, in the present study, we wanted to examine the effects of ferulic acid on the APP/PS1 double transgenic mice, extending our previously study on the protective effects of ferulic acid against the i.c.v. administered Aβ toxicity.
8-10)
MATeRIAlS AND MeTHODSMice and Ferulic Acid Female APP/PS1 (APPswe/ PS1de9) transgenic mice were obtained from Jackson laboratory (Bar Harbor, Me, U.S.A.). Procedures for animal experiments were approved by the Animal experimentation Committee at Hallym University. Ferulic acid was obtained from Sigma Chemical Co. (St. louis, MO, U.S.A.). Because 0.004% and 0.006% of ferulic acid in the drinking water (with the average water intake per mouse per day of about 6-8 ml) found to be effective in our previous study on the the protective effects of long-term administration of ferulic acid against the in vivo toxicity of β-amyloid peptide administered intracerebroventricularly in mice [8][9][10] was approximately 9-13 mg/kg/d (for 0.004%) and 14-19 mg/kg/d (for 0.006%), we chose the ferulic acid doses of 5.3 and 16 mg/kg/d in the present study. Ferulic acid was administered from 6 months of age for 6 months at 2 different doses (5.3 ...