The protective effect of biotin supplementation and swimming training on cognitive impairment and mental symptoms in a rat model of Alzheimer's disease: A behavioral, biochemical, and histological study

Abstract

Vitamin B (Vit B) plays a regulatory role in cognitive memory and learning. We examined the biochemical and behavioral effects of biotin supplementation (BS) and swimming training (ST) on Alzheimer's disease (AD), the most common type of dementia, in male rats. Sixty rats were randomly assigned to six groups: control, sham (receiving phosphate-buffered saline), AD (receiving a single injection of Aβ into the lateral ventricle), ST (for 28 days and before Aβ injection), and BS (receiving BS through oral gavage for 28 days before Aβ injection). The treatments were continued until the end of the behavioral tests. Learning and memory functions were investigated through the Morris water maze (MWM) and depression and anxiety-like behaviors were tested by elevated plus-maze (EPM) and forced swimming tests. In addition, oxidative stress biomarkers, such as total thiol groups (TTG) and malondialdehyde (MDA) in serum were assessed and histological studies were performed using brain tissues. In the AD group, Aβ increased the distance traveled and escape latency in the MWM, but co-administration of BS and ST attenuated the results of the MWM, EPM, and FST tests. Furthermore, BS decreased the litigious biochemical effects of Aβ by enhancing the levels of TTG, in addition to reducing serum MDA levels. The use of BS as a potent antioxidant improved Aβ-induced memory impairment. It attenuated oxidative stress biomarkers in the brain (number of Aβ plaques) and serum of AD rats. We provide evidence for the use of BS in neurodegenerative disorders, such as AD, to elucidate the possible mechanisms.

Keywords: Alzheimer's disease; Aβ plaque; Biotin supplementation; Swimming training.

Graphical abstract

Fig. 1

The experimental design.

Fig. 2

Morris water maze (MWM) test results. Escape latency a, traveled distance b, the mean time spent in the target quadrant c. Sham group: the rats that received phosphate-buffered saline (PBS); Alzheimer's group (AD) (biotin supplementation (BS) + Aβ): the rats that received BS for 28 days before Aβ injection; swimming training (ST) + Aβ group: the rats that performed ST for 28 days before Aβ injection, and BS + ST + Aβ group: the rats that received both BS and ST before Aβ injection. Data are shown as mean ± standard error of the mean (SEM). ***p < 0.001 compared to the control group and ###p < 0.001 compared to the AD group.

Fig. 3

Effects of the biotin supplementation (BS) and swimming training (ST) on the time spent in the open and closed arms (a) and open and closed arms entries (b) in the experimental groups using the elevated plus-maze test. Sham group: the rats that received phosphate-buffered saline (PBS); AD: Alzheimer's group (BS + Aβ): the rats that received BS for 28 days before Aβ injection; ST + Aβ group: the rats that performed ST for 28 days before Aβ injection; and BS + ST + Aβ group: the rats that received BS and ST before Aβ injection. Values are presented as mean ± SEM (n = 10 animals per group). ***p < 0.001 compared to the control group and #p < 0.05 and ###p < 0.001 compared to the AD group.

Fig. 4

Assessment of anxiety-like behaviors. Effects of the biotin supplementation (BS) and swimming training (ST) on floating, struggling, and swimming time in the experimental groups within 6 min in the forced swimming test. Sham group: the rats that received phosphate-buffered saline (PBS); AD: Alzheimer's group (BS + Aβ): the rats that received BS for 28 days before Aβ injection; ST + Aβ group: the rats that performed ST for 28 days before Aβ injection; and BS + ST + Aβ group: the rats that received BS and ST before Aβ injection. Values are presented as mean ± S.E.M for 10 rats. *p < 0.05, **p < 0.01, and ***p < 0.001 compared to the control group and ##p < 0.01 and ###p < 0.001 compared to the AD group.

Fig. 5

Plasma levels of total thiol groups (TTG) and malondialdehyde (MDA) in all groups. Sham group: the rats that received phosphate-buffered saline (PBS); AD: Alzheimer's group (BS + Aβ): the rats that received BS for 28 days before Aβ injection; ST + Aβ group: the rats that performed ST for 28 days before Aβ injection; and BS + ST + Aβ group: the rats that received BS and ST before Aβ injection. Data are presented as mean ± SEM (n = 10 per group). ***p < 0.001 compared to the control group and ###p < 0.001 compared to the AD group.

Fig. 6

H&E (two left columns) and Congo Red (two right columns) staining of the sections of the hippocampal CA1 region. Control (a), Sham (b), AD (c), BS + Aβ (d), ST + Aβ €, BS + ST + Aβ (f) groups. Sham group: the rats that received phosphate-buffered saline (PBS); AD: Alzheimer's group (BS + Aβ): the rats that received BS for 28 days before Aβ injection; ST + Aβ group: the rats that performed ST for 28 days before Aβ injection; and BS + ST + Aβ group: the rats that received BS and ST before Aβ injection ( × 40 and × 400). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 7

Effect of treatments on the number of amyloid plaques and the neuronal survival rate in the hippocampus (CA1) using Congo Red and H&E staining. Control (a), Sham (b), AD (c), BS + Aβ (d), ST + Aβ €, BS + ST + Aβ (f) groups. Sham group: the rats that received phosphate-buffered saline (PBS); AD: Alzheimer's group (BS + Aβ): the rats that received BS for 28 days before Aβ injection; ST + Aβ group: the rats that performed ST for 28 days before Aβ injection; and BS + ST + Aβ group: the rats that received BS and ST before Aβ injection. The black arrows in the right pitchers indicate pyramidal cells and the black arrow in the left pitchers shows amyloid plaques in the hippocampal CA1 region. Data are presented as mean ± S.E.M (n = 10 for each group). ***p < 0.001 compared to the control group and ###p < 0.001 compared to the AD group. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)