Acta Academiae Medicinae Sinica

Abstract:

Objective To explore the apoptosis in the hippocampus of dysbindin-1B^+/+ mice and the behaviors of 4-month-old dysbindin-1B^+/+ mice and wild-type mice. Methods The hippocampus of dysbindin-1B^+/+ mice and corresponding wild-type mice were assessed by TUNEL assay and transmission electron microscopy. Then twelve 4-month-old male dysbindin-1B^+/+ mice and twelve wild-type mice were enrolled. The open field and T maze test were conducted to observe locomotor activity,exploratory behaviors,and spatial memory. Result TUNEL⁺ neurons were found in hippocampus of dysbindin-1B^+/+ mice,especially in dentate gyrus region,but not in that of wild-type mice(t=12.98,P<0.0001). Transmission electron microscopy showed the presence of middle-and late-stage apoptosis in the hippocampus of dysbindin-1B^+/+ mice,while there was no apoptosis in wild-type mice. Open field test showed that,compared with the moving distance of wild-type mice [(3632±606)cm],dysbindin-1B^+/+ mice presented significantly lower moving distances [(2887±376)cm] (t=2.993,P=0.0122). Meanwhile,compared with the moving time of wild-type mice in the central area [(114.00±34.09)s],dysbindin-1B^+/+ mice presented lower moving time [(64.22±14.67)s] (t=4.649,P=0.0023). T maze test showed that when the interval between forced run and test run were 60 s and 180 s,respectively,the accuracy of dysbindin-1B^+/+ was (70.40±15.17)% and (59.28±9.10)%,which was significantly lower than those of wild type mice (91.67±13.94)% (t=3.261,P=0.0258) and (83.33±14.89)% (t=3.687,P=0.0291);when the interval was 15 s,there was no significant difference between these two groups [100% vs.(94.45±6.08)%; t=0.851,P=0.0756]. Conclusion Dysbindin-1B^+/+ expression can cause the apoptosis of neurons,which may cause anxious behavior and impair the locomotor activity and spatial memory.

Key words: dysbindin-1, apoptosis, locomotor activity, exploratory behavior, cognition impairment