The Effects of High Dose Vitamin D on Motor Learning and Seizures in a Mouse Model of Hyperactive Mtor Induced Epilepsy
Abstract number :
3.346
Submission category :
10. Dietary Therapies (Ketogenic, Atkins, etc.)
Year :
2022
Submission ID :
2204227
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Authors :
David Narvaiz, MA – Baylor University; Katherine Blandin, BS – Baylor University; Srikhar Chilukuri, none – Baylor University; Kylie Dimond, none – Baylor University; Grace O'Neill, none – Baylor University; Jacob Pilcher, none – Baylor University; Paige Womble, MA – Baylor University; Joaquin Lugo, PhD – Baylor University
Rationale: Genetic mutations that cause hyperactive mechanistic target of rapamycin (mTOR) signaling in the cerebellum lead to disrupted cerebellar signaling, debilitating motor impairments, and may contribute to the development of epilepsy. Recent studies have demonstrated that the mTOR inhibitor rapamycin can reduce mTOR signaling and reduces seizures; however, long-term use of rapamycin can produce non-specific effects. Thus, a critical need for better therapies to treat individuals with hyperactive mTOR induced motor impairments and epilepsy remains. Vitamin D is a safe, over-the-counter supplement that has been shown to suppress mTOR signaling and abate seizure severity. However, it has not been determined if vitamin D can ameliorate the development of motor impairments and epilepsy induced by hyperactive mTOR signaling. Here, we determine the effects of supplemental vitamin D in a mouse model of hyperactive mTOR induced epilepsy and ataxia.
Methods: Male and female neuronal subset specific Pten knockout (KO) and wildtype (WT) mice were provided either a diet supplemented with 20,000 IU/g of vitamin D3 or a standard mouse chow containing 1,500 IU/g of vitamin D3 starting at 4 weeks and were maintained on the diet for the remainder of the experiment. At 6 weeks, mice underwent testing for motor coordination and motor learning in the sticker removal and rotarod tests. Mice were then recorded 1 hour a day for 5 days on weeks 9 and 10 to determine the time to the first seizure, seizure frequency, and the total duration of time spent seizing.
Results: Our preliminary data show KO mice exhibit an increased latency to remove a sticker compared to WT mice, independent of diet, p < .01. KO mice on the standard diet, but not the vitamin D diet, required more attempts to remove the sticker compared to WT mice, p < .05. On the rotarod test, KO mice spent less time on the rotarod compared to WT mice, p < .001; with no effect of vitamin D. The time until a seizure was detected was greater in KO mice on the vitamin D diet compared to KO mice on the standard diet, p < .05. There was no effect of vitamin D on the frequency or total duration of seizures exhibited.
Dietary Therapies (Ketogenic, Atkins, etc.)