A vitamin D enriched diet attenuates sex-specific behavioral deficits, increases the lifespan, but does not rescue bone abnormalities in a mouse model of cortical dysplasia.

Individuals who experience recurrent spontaneous seizures often show behavioral and physiological comorbidities. Those with epilepsy are at a high risk of bone fractures (independent of seizure-related falls) and show a higher rate of a diagnosis of Autism Spectrum Disorder. The neural subset-specific (NS) Pten knockout (KO) mouse has an epilepsy phenotype, has been characterized to show autistic-like deficits, and has an osteoporosis phenotype. The current study examined the effect of a vitamin D enriched diet (20,000 IU VD) in the NS-Pten KO and wildtype mice. Mice were placed onto a vitamin D enriched diet at 4 weeks of age and maintained on that diet throughout testing. Behavioral testing began at 6 weeks of age and included tests for general activity, anxiety, repetitive behaviors, social behaviors, and memory. Results indicated that a vitamin D diet attenuated hypoactivity levels in male KO mice (p < 0.05). In a social partition task, vitamin D increased sociability in male wildtype mice, (p < 0.05). Most significantly, vitamin D fortified diet increased percent survival in KO animals and decreased the level of microglia marker IBA-1 and mTOR (mammalian target of rapamycin) downstream targets pS6 and pAKT. A high vitamin D diet did not reverse bone deficits in male or female KO mice. Overall, these findings suggest that a vitamin D enriched diet had a significant impact on the behavioral phenotype of NS-Pten KO mice, suggesting that dietary manipulations could be a potential therapeutic option for autistic-like behavior.

Lipopolysaccharide-induced sickness behavior is not altered in male Fmr1-deficient mice.

OBJECTIVES: Fragile X syndrome is the main monogenetic cause of intellectual disability and autism. Alterations in the immune system are commonly found in these developmental disorders. We and others have demonstrated that Fmr1 mutant mice present an altered response to immune stimuli. However, whether this altered immune response can influence the Fmr1 mutant behavioral outcomes in response to inflammation has not been fully investigated. MATERIALS AND METHODS: In the current study, we examine the behavioral sickness response of male wildtype and knockout  mice to the innate immune stimulus lipopolysaccharide (LPS) (0.1 mg/kg) to determine if Fmr1 mutants have altered sickness behavior. We used an enzyme-linked immunosorbent assay (ELISA) to measure changes in the cytokine interleukin-6 (IL-6) to determine that inflammation was induced in the mice. Sickness behavior was assessed in a wheel-running paradigm, and a tail suspension test was used to assess the depressive-like phenotype that follows sickness behavior in response to LPS. RESULTS: The ELISA using blood serum confirmed a significant increase in IL-6 in mice that were treated with LPS. Treated Fmr1 mutants exhibited decreased distance traveled in the wheel running after LPS administration, similar to treated controls. Another cohort of animals treated with LPS were tested in the tail suspension test and exhibited no alterations in immobility time in response to LPS. CONCLUSION: Together, our data suggest that Fmr1 mutant mice do not have altered sickness behavior in response to a low dose of LPS.

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.