Restoration of Spatial Learning Through Oral Administration of Lipopolysaccharides in Diabetes-related Cognitive Dysfunction

(A) Protocol of the preventive experiment. STZ was administered icv 1 week after continuous OAL, and three weeks later, learning and memory abilities in mice with STZ-induced DRCD were evaluated using the MWM. OAL: Oral administration of LPS from P. agglomerans; BW: body weight; DRCD: diabetes-related cognitive dysfunction; LPS: lipopolysaccharide; MWM: Morris water maze; icv: intracerebroventricularly; po: per os. (B) Protocol of the treatment experiment. STZ was administered intracerebroventricularly on Day 0 to the STZ groups. An equivalent amount of saline was administered icv to the saline group. The first MWM was started on Day 13 to confirm that DRCD had been induced in the STZ. The STZ group was divided into STZ and STZ +LPS groups after the first MWM. LPS was added to the drinking water of the STZ +LPS group starting from Day 17 until the end of the experiment. The second MWM was started on Day 41. The spatial recognition ability of the STZ-induced DRCD mice compared to the saline control group was assessed using the MWM performed 13 days after STZ administration (the first MWM). (C) Escape latency of the STZ and saline groups during the 4 training days. (D) Average time spent in the target quadrant by the STZ and saline groups in the probe test. (STZ group, n=18, saline group, n=9). Data are presented as average±standard error of the mean. *p<0.01 for Student’s t-test.