Examination of the effect of a diet high in vitamin D in a preclinical model of fragile X syndrome.

Neurodevelopmental disorders affect approximately 17% of the population. Fragile X Syndrome (FXS) is a genetic neurodevelopmental disorder that is the most common form of inherited intellectual disability and is a monogenic cause of autism spectrum disorder (ASD). Individuals with FXS lack the ability to synthesize fragile x messenger ribonucleoprotein (FMRP), leading to pronounced behavioral and cognitive impairments such as deficits in communication, repetitive behaviors, and intellectual disabilities. Additionally, individuals with FXS exhibit molecular abnormalities, including dysregulation of the mammalian target of rapamycin (mTOR) and mGluR signaling cascades. Murine models of FXS resemble behaviorally and molecular characteristics of ASD, making this model a valuable tool for studying this disorder. Currently, there is no treatment for FXS, emphasizing the critical need for new interventions. Previously, vitamin D has been found to alleviate symptoms of ASD in children and aid in the regulation of mTOR. In the present study, we gave a high dose of dietary vitamin D (20,000 IU/Kg) to C57BL/6J FMR1 male wildtype and knockout mice. We found that the FMR1 knockout mice had alternations in movement, anxiety, exploratory, learning and memory, and sensory-motor gating behaviors. However, we found no rescue of behavioral impairments of FMR1 knockout mice in the open field, elevated plus maze, nose poke, social partition, delayed fear conditioning, nor prepulse inhibition task. There was no difference in weight between groups, but there was a difference in food intake finding that animals on the vitamin D diet consumed more food than animals on the control diet. We also looked at pS6, a downstream target of the mTOR pathway, but there were no differences found. More research is needed to find other alternatives to improve cognitive and behavioral outcomes of individuals with FXS.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Doctoral

Grantor

Baylor University.

Year dc:date.issued

2023

Author dc:creator

• Womble, Paige Deann, 1995-

Advisor dc:contributor.advisor

• Lugo, Joaquin N.

• Fragile X syndrome.
• Vitamin D.
• MTOR.

Statement dc:rights

• Baylor University works are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact libraryquestions@baylor.edu for inquiries about permission.

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/2104/12866

OAI identifier oai:identifier

oai:baylor-ir.tdl.org:2104/12866