Efficacy of the silicon based agent for age related decline in vestibular function

Abstract

Age-related vertigo and balance disorders can lead to falls, fractures, and prolonged confinement to bed. Loss of mobility and/or social interaction may cause cognitive decline and lower quality of life, resulting in significant social and economic burdens. Aging societies urgently need treatments for vestibular decline, as no cures exist, and current therapies only provide symptomatic relief. Oxidative stress contributes to age-related cochlear balance system damage, making antioxidants a potential treatment. Silicon-based agent (Si-agent) is an excellent antioxidant. When reacting with water, this agent produces hydrogen continuously, offering sustained antioxidant effects. Oral Si-agent has alleviated oxidative stress-related diseases in mouse models, such as ulcerative colitis and Parkinson's disease. This study evaluated Si-agent for age-related vestibular decline in mice. In balance beam tests, Si-agents-treated group showed less balance decline with age compared to untreated mice. However, vestibulo-ocular reflex (VOR) tests measuring semicircular canal and otolith organ function showed no significant differences. In linear VOR, no significant differences were observed at any frequency; however, a significant difference was found in the average slope of linear decline between 0.7 and 0.9 G. Structural damage to the inner ear's semicircular canals and otolith organs was also reduced in Si-agents-treated group. These findings suggest that Si- agent may help treat age-related in balance and motor decline.

Keywords: Aging; Decline in vestibular function; Oxidative stress; Si-based agent; Vestibulo-ocular reflex.

Fig. 1

(a–d) The bar graph shows average values of the duration to the goal (a,c) and the number of falls (b,d) in the balance beam test. (a,b) 20 mm rod and (c,d) 10 mm rod: bottom graphs. White: Con group (Con), Grey: Si group (Si). Data are expressed as the mean ± SEM of ten (Con) or twelve mice (Si) per group. *p < 0.05 vs. Con group, determined by Student’s paired t-test.

Fig. 2

(a) The photograph of the angular VOR (aVOR) analysis device. The mouse is fixed to the apparatus with a Z-shaped metal plate attached to its head. The movements of left eye and apparatus are recorded in a dark place using a high-speed infrared camera. (b) The line graph shows the aVOR means in the Con (black circle) and Si (square) groups when stimulated at 0.3 Hz, 1 Hz, and 2 Hz. Data are expressed as the mean ± SEM of sixteen mice per group. Results of the Student’s paired t-test showed no significant differences between the two groups.

Fig. 3

(a) Photograph of the linear VOR analysis device. The mouse is placed on the device that runs along a straight stainless-steel rail and three steps of linear acceleration stimuli (0.7 G: 3.06 m/s, 0.9 G: 3.25 m/s and 1.3 G: 3.25 m/s) are applied. Eye movements are recorded in a dark place using a high-speed infrared camera. (b,c) The line graph shows the lVOR means in the Con (black circle) and Si group (square) when stimulated at 0.7 G, 0.9 G, and 1.3 G in the interaural axis (b) and the naso-occipital axis direction (c). Data are expressed as the mean ± SEM of sixteen mice per group. Results of the Student’s paired t-test showed no significant differences between the two groups.

Fig. 4

(a–d) The line graphs of the individual lVOR in the Con (a,c) and Si groups (square) when stimulated at 0.7 G, 0.9 G, and 1.3 G in the interaural axis (a,b) and the naso-occipital axis direction (c, d). (e–h) The bar graphs of the average slope of the line connecting the eye deviation angles from 0.72 to 0.89 G (e,g) and from 0.89 to 1.31 G (f,h) in the interaural axis (e, f) or the naso-occipital axis direction (g,h). Data are expressed as the mean ± SEM of sixteen mice per group. *p < 0.05 vs. Con group, determined by Student’s paired t-test.

Fig. 5

(a–l) Representative examples of HE-stained images of the LSCC (a,d), the ASCC (b,e), the PSCC (c,f), the utricle (g,j), the saccule (h,k), and the VG (i,l) in the Con (a–c, g–i; twelve mice) and Si groups (d–f, j–l; twelve mice). LSCC: lateral semicircular canal. ASCC: anterior semicircular canal. PSCC: posterior semicircular canal. VG; vestibular ganglion. Arrows: vacuolation of the cytoplasm of hair cells and Arrowheads: hair cell loss. Scale bar: 20 µm. (m–p) The bar graph shows average values of the cytoplasmic vacuolation (upper) and cell loss (bottom) in the hair cells of the LSCC (m), ASCC (n), Utricle (o) and Saccule (p). White: Con group (Con), Grey: Si group (Si). Data are expressed as the mean ± SEM of ten-twelve (Con) or eight-twelve mice (Si) per group, determined by Student’s paired t-test. No significant differences were detected between Con and Si group.

Fig. 6

(a,b) Representative micrographs of immunostaining using Oncomodulin (a) and Calretinin antibody (b) of the LSCC (left), the utricle (middle) and the saccule (right) in the Con (upper; five mice) and Si groups (bottom; five mice). LSCC: lateral semicircular canal. Arrows: immunopositive cells. Scale bar: 20 µm.