Vitamin D Supplementation Partially Rescues Breathing Deficits in Mecp2 Hemizygous Null Mice, a Model of Rett Syndrome

• DOI: 10.1096/fasebj.2022.36.s1.r3831
• Publication Date: 2022-05-03T08:48:22Z
• Authors: Lara R. DeRuisseau; Lyna Mora; Ash Zheng; B. S. Amin; Samuel O. Bonsu; Burak T. Cilhoroz; Keith C. DeRuisseau; Angelica M. Kowal...; Jessica L. MacDonald
• Keywords: Rett Syndrome; MeCP2

Rett syndrome (RTT) is a severe X-linked progressive neurodevelopmental disorder affecting ~1 in 10,000 females. It the second most common genetic cause of cognitive disability girls, after Down syndrome. Girls with this devastating develop relatively normally for 6-18 months, which they undergo period rapid regression. They lose many motor skills, growth their brain slows, and repetitive, autistic behaviors seizures. Autonomic disruptions are leading early death RTT, rescue breathing deficits considered primary goal development therapeutic interventions. We initiated proof-of-concept study by investigating male Mecp2 hemizygous null mice as have strongest phenotype occurs at an age; Mecp2-null (KO) also been characterized thoroughly literature. tested hypothesis that Vitamin D supplementation (VitD) would ameliorate, or partially cardiovascular KO mice. Mice were 4 weeks age (PRE), then placed on control (1 IU D/g) VitD (50 diet, re-tested 8 (POST). To examine our hypothesis, unrestrained barometric plethysmography was used to quantify frequency (breaths/min), tidal volume (VT; mL/breath), VT/inspiratory time (VT/Ti; mL/sec), minute ventilation (VE; mL/min/g) ventilatory equivalent CO2 (VE/VCO2) both wildtype (WT; n=6) (n=5) littermates. Data Sciences International Ponemah software analyze flow tracings during exposure air (20.93% O2, balanced N2). The MouseOx Plus STARR Life utilized collect heart rate (HR) oxygen saturation freely moving conscious expressed mean ± S.D., WT vs. KO. In PRE group, had dysregulated HR previously demonstrated literature (data not shown). POST diet groups, VT (0.24±0.02 vs 0.15±0.06 mL/breath; p=0.01) VT/Ti remained lower (2.085±0.313 1.291±0.583 mL/sec; p=0.017) However, (166±21 166±19 breaths/min), VE/g (1.07±0.12 0.99±0.57 mL/min/g), ratio VE/VCO2 (112±47 103±46) (582±84 532±59 beats/min) similar between number desaturations significant KO, but values variable across groups included (12±7 5±7 desaturations/30 minutes), findings we described young These data reveal partial following VitD. reduced suggests attenuated neural drive breath persists Current studies examining responses hypoxia hypercapnia will identify more information about carbon dioxide sensing these diets.