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. 2021 May 7:8:667587.
doi: 10.3389/fnut.2021.667587. eCollection 2021.

Juvenile Selenium Deficiency Impairs Cognition, Sensorimotor Gating, and Energy Homeostasis in Mice

Victor W Kilonzo  1 , Alexandru R Sasuclark  1 , Daniel J Torres  2 , Celine Coyle  1 , Jennifer M Pilat  3 , Christopher S Williams  3 , Matthew W Pitts  1
Affiliations

Juvenile Selenium Deficiency Impairs Cognition, Sensorimotor Gating, and Energy Homeostasis in Mice

Victor W Kilonzo et al. Front Nutr. .

Abstract

Selenium (Se) is an essential micronutrient of critical importance to mammalian life. Its biological effects are primarily mediated via co-translational incorporation into selenoproteins, as the unique amino acid, selenocysteine. These proteins play fundamental roles in redox signaling and includes the glutathione peroxidases and thioredoxin reductases. Environmental distribution of Se varies considerably worldwide, with concomitant effects on Se status in humans and animals. Dietary Se intake within a narrow range optimizes the activity of Se-dependent antioxidant enzymes, whereas both Se-deficiency and Se-excess can adversely impact health. Se-deficiency affects a significant proportion of the world's population, with hypothyroidism, cardiomyopathy, reduced immunity, and impaired cognition being common symptoms. Although relatively less prevalent, Se-excess can also have detrimental consequences and has been implicated in promoting both metabolic and neurodegenerative disease in humans. Herein, we sought to comprehensively assess the developmental effects of both Se-deficiency and Se-excess on a battery of neurobehavioral and metabolic tests in mice. Se-deficiency elicited deficits in cognition, altered sensorimotor gating, and increased adiposity, while Se-excess was surprisingly beneficial.

Keywords: cognition; energy metabolism; neurodevelopment; selenium; sensorimotor gating.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Assessment of varying Se supplementation on organ-specific Se content, glutathione peroxidase activity, and selenoprotein levels. (A) Mean (±SEM) daily food intake. (B) Mean (±SEM) daily water consumption. (C) Mean (±SEM) daily selenium intake (n = 6–7 per group). (D) Mean (±SEM) selenium content in kidney, liver, testes, serum, and brain (n = 3–4 per group). (E) Mean (±SEM) GPX activity in liver, serum, and brain (n = 4 – 6). (F–I) Protein levels of GPX1, TXNRD2, and SELENBP1 in liver (F,G) and brain (H,I) (n = 4). $$p < 0.01 between Se-exc and Se-sup groups; *p < 0.05 between Se-exc and Se-def groups; **p < 0.01 between Se-exc and Se-def groups; #p < 0.05 between Se-def and Se-sup groups; ##p < 0.01 between Se-def and Se-sup groups.
Figure 2
Figure 2
Se-deficient mice exhibit deficits in cognition and sensorimotor gating. (A) Mean (±SEM) number of incorrect holes checked before locating the escape tunnel during Barnes maze training. (B) Mean (±SEM) latency to locate the escape tunnel during maze training. (C) Mean (±SEM) latency to fall off the Rotarod at 8, 12, and 16 weeks of age. (D) Mean (±SEM) normalized startle magnitude as a function of acoustic startle intensity. (E) Mean (±SEM) percentage of prepulse inhibition as a function of prepulse intensity above the background level (70 dB). $p < 0.05 between Se-exc and Se-sup groups; *p < 0.05 between Se-exc and Se-def groups; **p < 0.01 between Se-exc and Se-def groups; #p < 0.05 between Se-def and Se-sup groups (n = 9–10 animals per group for all experiments).
Figure 3
Figure 3
Impaired glucose tolerance and increased adiposity in Se-deficient mice. (A) Mean (±SEM) blood glucose levels during glucose tolerance testing (n = 7–8 per group). (B) Mean (±SEM) body weight from 4 to 20 weeks of age (n = 9–10). (C) Mean (±SEM) inguinal white adipose tissue (n = 4). (D) Mean (±SEM) gonadal white adipose tissue relative to total body weight (n = 4). (E) Mean (±SEM) serum leptin levels (n = 7–9). (F) Representative images of brown adipose tissue (BAT). (G) Scatter plot of BAT lipid droplet size (n = 4). Scale bar = 100 μm, *p < 0.05 between Se-exc and Se-def groups, **p < 0.01 between Se-exc and Se-def groups; ##p < 0.01 between Se-def and Se-sup groups.
Figure 4
Figure 4
Influence of varying Se supplementation on locomotion and respiratory metabolism. (A) Mean (±SEM) locomotor activity during the light and dark cycles. (B) 48-h time course of locomotor activity. (C) Mean (±SEM) energy expenditure during the light and dark cycles. (D) Mean (±SEM) respiratory quotient during the light and dark cycles. $p < 0.05 between Se-exc and Se-sup groups; $$p < 0.01 between Se-exc and Se-sup groups; (n = 6–7 animals per group for all experiments).
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