1331-P: Correlation between Sleep Deduction and Neurobehavioral Deficits in the Mouse Offspring of Mother with Diabetes

Lines of human cohort studies reported increased risk of neurobehavioral abnormalities as well as sleep problems in offspring of mother with diabetes (OMD). Preclinical studies demonstrated that forced sleep disturbance leads to poor cognitive function in mice. Based on these findings, our hypothesis posits that wide spectrum of neurobehavior issues in OMD is due to their sleep disturbance. To test this hypothesis, we first established mouse OMD models for examining the correlation between sleep disturbance and performance in a battery of neurobehavior tests. Female C57BL/6 mice received intraperitoneal injection of Streptozocin at 6 weeks old. DM was confirmed before start of mating. OMD in juvenile were placed to neurobehavior tests as well as piezoelectric sensor system of sleep under 12 h light/12 h dark cycles. In open field test, OMD spent significantly more time in the center of the field, suggesting the increased risk-taking behavior or/and reduced anxiety. Interestingly, several rodent models of autism showed similar behavior changes, and human OMD patients have increased risk of autism. Furthermore, the change of the behavior in our model was augmented in male and this may be consistent with the human OMD in which male patients has higher risk of autism than female. In water T maze test, the ability of spatial learning in OMD was comparable to that of control animals, while the reversal learning was impaired. Sleep time of OMD was significantly shorter than that of control in both dark and light phases. We also found positive correlation between sleep time and cognitive flexibility that was measured as reversal learning level in water T maze. However, the proxy for risk taking behavior did not show correlation with the sleep time. Altogether, our results demonstrate the correlation between sleep disturbance and impaired cognitive flexibility, and thus shed light on the potential mechanisms underlying intellectual disability that is frequently observed in OMD. Disclosure K. Sugai: None. J. Sasaki: None. M. Odawara: Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo, Eli Lilly Japan K.K., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. M. Torii: None. K. Hashimoto-Torii: None. Funding Scott-Gentle Foundation