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

• Published in: Epilepsy & behavior Vol. 124; p. 108297
• Main Authors: Womble, Paige D., Hodges, Samantha L., Nolan, Suzanne O., Binder, Matthew S., Holley, Andrew J., Herrera, Rebecca, Senger, Savannah, Kwok, Eliesse, Narviaz, David A., Faust, Amanda, Hernandez-Zegada, Christian J., Kwon, Ronald Y., Lugo, Joaquin N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2021
• Subjects: Autism; Bone density; Epilepsy; Fortified diet; Seizures; Supplement; Fortified diet; Supplement; Autism; Bone density; Epilepsy; Seizures
• DOI: 10.1016/j.yebeh.2021.108297
• EISSN: 1525-5069
• ISSN: 1525-5050

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•Vitamin D enriched diet attenuated hypoactivity and rearing in the open-field test.•Vitamin D enriched diet increased percent survival in male and female NS-Pten KO mice.•Vitamin D enriched diet did not reverse bone deficits in the NS-Pten KO animals.•Vitamin D enriched diet did not decrease pS6 or pAKT levels compared to mice on the CTL diet.
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.