Protective effects of selegiline against amyloid beta-induced anxiety-like behavior and memory impairment

Abstract

Background: Alzheimer's disease (AD) is a complex and common neurodegenerative disorder. The present study aimed to investigate the potential effects of selegiline (SEL) on various aspects of memory performance, anxiety, and oxidative stress in an AD rat model induced by intracerebroventricular injection of amyloid beta_1-42 (Aβ_1-42).

Methods: Oral administration of SEL at a dose of 0.5 mg/kg/day was performed for 30 consecutive days. Following the 30 days, several tests, including the open-field, elevated plus-maze, novel object recognition, Morris water maze, and passive avoidance learning were conducted to assess locomotor activity, anxiety-like behavior, recognition memory, spatial memory, and passive avoidance memory, respectively.

Results: The results indicate that the induction of AD in rats led to recognition memory, spatial memory, and passive avoidance memory impairments, as well as increased anxiety. Additionally, the AD rats exhibited a decrease in total antioxidant capacity and an increase in total oxidant status levels, suggesting an imbalance in oxidative-antioxidant status. However, the administration of SEL improved memory performance, reduced anxiety, and modulated oxidative-antioxidant status in AD rats.

Conclusions: These findings provide evidence that SEL may alleviate anxiety-like behavior and cognitive deficits induced by Aβ through modulation of oxidative-antioxidant status.

Keywords: alzheimer's disease; anxiety; oxidative stress; passive avoidance memory; selegiline; spatial memory.

FIGURE 1

After a week of acclimation, the rats in the AD and AD + SEL groups received A 5‐µL solution of Aβ_1‐42 (1 mg/mL). SEL at a dose of 0.5 mg/kg/day was then orally administered to the SEL and AD + SEL groups for 30 days. Subsequently, anxiety, recognition, spatial, and passive avoidance tests were performed. At the end of the experiment, plasma levels of total antioxidant capacity (TAC) and total oxidative stress (TOS) were measured. EPM, elevated plus‐maze; MWM, Morris water maze; NOR, novel object recognition; NOT, number of trials to reach learning; OF, open‐field; PAL, passive avoidance learning; STLa, step‐through latency in the acquisition trial; STLr, step‐through latency in the retention phase; TDC, time spent in the dark compartment.

FIGURE 2

Samples of recorded activities of rats in the OF test (a). Effects of selegiline on locomotor activity in the open‐field test (b) and the discrimination index of the novel objective recognition (c) of rats. Data are presented as means ± SD of eight animals per group (one‐way analysis of variance). ns, no significance; *p < .05, **p < .01, ***p < .001. AD, Alzheimer's disease; PBS, phosphate‐buffered saline; SEL, selegiline.

FIGURE 3

Samples of recorded activities of rats in the elevated plus‐maze (EPM) test (a). The effects of selegiline administration on the open arms entries (b), time spent in open arms (c) of the elevated plus maze Test. Data are presented as means ± SD of eight animals per group (one‐way analysis of variance, Tukey's post hoc test). **p < .01, ***p < .001. AD, Alzheimer's disease; PBS, phosphate‐buffered saline; SEL, selegiline.

FIGURE 4

The effects of selegiline administration on the swimming distance (a) and escape latency (b) to the hidden platform in the training trials, and time spent in target zone (c) in the Morris water maze Test. Data are presented as means ± SD of eight animals per group (two‐ and one‐way analysis of variance, Tukey's post hoc test). ns, no significance; *p < .05, **p < .01, ***p < .001. AD, Alzheimer's disease; PBS, phosphate‐buffered saline; SEL, selegiline.

FIGURE 5

The effects of selegiline administration on passive avoidance learning (PAL) in the Aβ rats (n = 8). “a” represents step‐through latency in the acquisition trial (STLa) and presented as means ± SD (one‐way analysis of variance). “b,” “c,” and “d” represents the number of trials to reach learning (NOT), step‐through latency in the retention phase (STLr), and time spent in the dark compartment (TDC), respectively. Data are presented as the median interquartile range (Kruskal–Wallis test, Dunn's post hoc test). ns, no significance; *p < .05, **p < .01, and ***p < .001. AD, Alzheimer's disease; PBS, phosphate‐buffered saline; SEL, selegiline.

FIGURE 6

The effects of selegiline administration on the plasma parameters of total oxidant status (TOS) (a) and total antioxidant capacity (TAC) (b) of AD rats using assay kits. Data are presented as means ± SD of eight animals per group (one‐way analysis of variance, Tukey's post hoc test). **p < .01, ***p < .001. AD, Alzheimer's disease; PBS, phosphate‐buffered saline; SEL, selegiline.