Edible Bird's Nest Prevents Menopause-Related Memory and Cognitive Decline in Rats via Increased Hippocampal Sirtuin-1 Expression

Abstract

Menopause causes cognitive and memory dysfunction due to impaired neuronal plasticity in the hippocampus. Sirtuin-1 (SIRT1) downregulation in the hippocampus is implicated in the underlying molecular mechanism. Edible bird's nest (EBN) is traditionally used to improve general wellbeing, and in this study, we evaluated its effects on SIRT1 expression in the hippocampus and implications on ovariectomy-induced memory and cognitive decline in rats. Ovariectomized female Sprague-Dawley rats were fed with normal pellet alone or normal pellet + EBN (6, 3, or 1.5%), compared with estrogen therapy (0.2 mg/kg/day). After 12 weeks of intervention, Morris water maze (four-day trial and one probe trial) was conducted, and serum estrogen levels, toxicity markers (alanine transaminase, alkaline phosphatase, urea, and creatinine), and hippocampal SIRT1 immunohistochemistry were estimated after sacrifice. The results indicated that EBN and estrogen enhanced spatial learning and memory and increased serum estrogen and hippocampal SIRT1 expression. In addition, the EBN groups did not show as much toxicity to the liver as the estrogen group. The data suggested that EBN treatment for 12 weeks could improve cognition and memory in ovariectomized female rats and may be an effective alternative to estrogen therapy for menopause-induced aging-related memory loss.

Figure 1

Effect of EBN on MWM performance in the spatial memory acquisition phase. All values are expressed as mean ± SEM for 6 animals in each group. Sham: surgically opened but not ovariectomized and fed with standard rat chow for 12 weeks. OVX: ovariectomized and fed with standard rat chow for 12 weeks; estrogen: ovariectomized and fed with standard rat chow and 0.2 mg/kg body weight of estrogen for 12 weeks; EBN high, medium, and low: ovariectomized and fed with standard rat chow and 1.2, 0.6, and 0.3 g/kg body weight of EBN/day, respectively, for 12 weeks.

Figure 2

(a) Representative path tracings of the Morris water maze. A: sham group (A1, first day first trial; A2, probe trial); B: OVX group (B1, first day first trial; B2, probe trial); C: estrogen group (C1, first day first trial; C2, probe trial); D: EBNH group (D1, first day first trial; D2, probe trial); E: EBNM group (E1, first day first trial; E2, probe trial); F: EBNL group (F1, first day first trial; F2, probe trial). (b) Time in the target quadrant in the probe trial; (c) latency to the first entry to the target quadrant. ^AP < 0.05 compared with OVX group; ^BP < 0.05 compared with sham group for spending time in the target quadrant and latency to the first entry to the target quadrant (ANOVA). OVX: ovariectomized. Groups are the same as in Figure 1.

Figure 3

Liver enzymes and kidney function. (a) Serum ALT activity; (b) serum ALP activity; (c) serum creatinine activity; (d) serum urea activity. Data are expressed as mean ± SEM of six animals. ^AP < 0.01 compared with estrogen group. Groups are the same as in Figure 1.

Figure 4

SIRT1 immunoreactivity in the pyramidal layer of the hippocampus (100x). Representative micrographs of SIRT1 (n = 6) show the pyramidal layer of the hippocampus. The age-associated reduction in SIRT1 immunoreactivity is attenuated by OVX and ameliorated by EBN treatment. Groups are the same as in Figure 1.

Figure 5

SIRT1 immunoreactivity in the dentate gyrus (100x). Representative micrographs of SIRT1 (n = 6) in the dentate gyrus demonstrate that the age-associated reduction in SIRT1 immunoreactivity is attenuated by OVX and ameliorated by EBN treatment. Groups are the same as in Figure 1.

Figure 6

Bar graphs showing the optical density (OD) of SIRT1 immunoreactivity in the pyramidal layer (a) and dentate gyrus (b). ^AP < 0.05 compared with OVX; ^BP < 0.05 compared with sham operation group; ^CP < 0.05 compared with estrogen; ^DP < 0.05 compared with EBN group. Groups are the same as in Figure 1.