Vitamin D supplementation positively affects activity but impairs stimulus response behavior in an age and sex specific manner in C57BL/6 mice.

Several studies have begun to demonstrate the possible cognitive and physiological benefits of a fortified vitamin D diet. However, the behavioral effects of a high vitamin D fortified diet during adolescence has not been fully explored. In the present study, a 4-week vitamin D fortified diet (20,000 IU/Kg) compared to controls (1500 IU/Kg) was administered during the juvenile (4 weeks old) or early adult period (8 weeks old) in C57BL/6 J mice to investigate the effects of fortification on cognition, behavior, and their bone phenotype. After 4 weeks on the diet, vitamin D-treated and control groups underwent a 4-week battery of behavioral tests while remaining on their respective diets. We found that a fortified diet affected behavior in both an age- and sex-specific manner. When vitamin D was administered to juveniles, both sexes displayed impaired habituation to a loud tone. However, females also presented with impaired prepulse inhibition compared to female controls. In the adult treated group, the fortified diet increased only time spent in the open field and had no effect on anxiety-like behavior in the elevated plus maze. Juvenile mice treated with a high vitamin D fortified diet showed a decrease in the total volume compared to the control group in the proximal metaphysis and midshaft region of their femur. There were no differences in bone measurements for mice treated during adulthood. Overall, our results suggest that the juvenile period is a more sensitive time point to the startle response and bone effects of a diet supplemented with high vitamin D, while adults exhibited alterations in locomotive behavior.

Rapamycin, but not minocycline, significantly alters ultrasonic vocalization behavior in C57BL/6J pups in a flurothyl seizure model.

Epilepsy is one of the most common neurological disorders, with individuals having an increased susceptibility of seizures in the first few years of life, making children at risk of developing a multitude of cognitive and behavioral comorbidities throughout development. The present study examined the role of PI3K/Akt/mTOR pathway activity and neuroinflammatory signaling in the development of autistic-like behavior following seizures in the neonatal period. Male and female C57BL/6J mice were administered 3 flurothyl seizures on postnatal (PD) 10, followed by administration of minocycline, the mTOR inhibitor rapamycin, or a combined treatment of both therapeutics. On PD12, isolation-induced ultrasonic vocalizations (USVs) of mice were examined to determine the impact of seizures and treatment on communicative behaviors, a component of the autistic-like phenotype. Seizures on PD10 increased the quantity of USVs in female mice and reduced the amount of complex call types emitted in males compared to controls. Inhibition of mTOR with rapamycin significantly reduced the quantity and duration of USVs in both sexes. Changes in USVs were associated with increases in mTOR and astrocyte levels in male mice, however, three PD10 seizures did not result in enhanced proinflammatory cytokine expression in either sex. Beyond inhibition of mTOR activity by rapamycin, both therapeutics did not demonstrate beneficial effects. These findings emphasize the importance of differences that may exist across preclinical seizure models, as three flurothyl seizures did not induce as drastic of changes in mTOR activity or inflammation as observed in other rodent models.