Abstracts

Rationale: Among the various behavioral and physiological comorbidities, individuals with epilepsy are at a high risk for bone fractures (independent of seizure-related falls), as well as an increased likelihood of a comorbid diagnosis of Autism spectrum disorder (ASD). There is also evidence that individuals with epilepsy are deficient in vitamin D levels. Prior work has shown that individuals with epilepsy have a reduced number of seizures when given a fortified vitamin D diet. For our studies, we used the neural subset-specific (NS) Pten knockout mouse, which is a model of Cortical Dysplasia, has been reported to have autistic-like deficits and lower bone mineral density. Methods: This current study examined the effect of a vitamin D enriched diet in the NS-Pten knockout mouse. Mice were placed onto a vitamin D enriched diet starting at 4 weeks of age and maintained on the diet throughout behavioral testing, which began at 6 weeks of age. Behavioral testing included tests for general activity, anxiety, repetitive behaviors, social behaviors, and learning and memory. Results: Results indicated that a vitamin D diet attenuated hyperactivity exhibited by the male knockout mice (p < 0.05). In the elevated plus maze task, knockout males showed increases in velocity and distance moved, which were attenuated by the vitamin D diet (p < 0.05). In the nose poke assay, knockout mice had a reduction in the number of holes poked compared to wildtype mice (p < 0.001), which was not attenuated by vitamin D. In a social partition task, male and female knockout animals exhibited a reduction in sociability, however in male wild type mice, vitamin D increased sociability (p < 0.05). During the conditioned stimulus test, there was a reduction in freezing in the knockout mice with the vitamin D diet compared to the knockout control mice (p < 0.05). Conclusions: Overall, these findings suggest that a vitamin D enriched diet attenuated hyperactivity and impacted learning and memory in the NS-Pten knockout mice. Funding: This work was supported by the National Institutes of Health (NIH) to JNL [Grant Number: NS088776].