Altered expression of gamma-secretase components in animal model of major depressive disorder induced by reserpine administration / 한국실험동물학회지

Altered expression of neurotrophic factors as well as neuroinflammation is commonly associated with Major depressive disorder (MDD) and Alzheimer's disease (AD). To investigate whether or not reserpine-induced MDD affects the expression of AD-related proteins, the expression of gamma-secretase components and substrate were measured in brains of ICR mice following reserpine treatment for 15 days. In active avoidance test, total response time and peak slightly increased in the 2 mg/kg reserpine (RSP2)-treated group compared to vehicle-treated group (P<0.05). Expression and phosphorylation of MKP-1, which is a key factor in MDD pathology, were both higher in the RSP2-treated group than the vehicle- and 1 mg/kg reserpine (RSP1)-treated groups (P<0.02). Furthermore, full-length expression of amyloid precursor protein (APP) was enhanced in the RSP1 and RSP2-treated groups compared to the vehicle-treated group, whereas expression of gamma-secretase components decreased (P<0.03). Among the three components of the gamma-secretase complex, nicastrin protein underwent the largest decrease in expression, as detected by Western blotting (P<0.03). Therefore, the data presented here provide additional evidence about the pathological correlation between MDD and AD.

Peroxiredoxin I regulates the component expression of gamma-secretase complex causing the Alzheimer's disease / 한국실험동물학회지

Peroxiredoxin I (Prx I) is a member of the peroxiredoxins (Prxs) family, which are antioxidant enzymes that regulate various cellular process via intracellular oxidative signal pathways. In order to investigate the correlation between Prx I and the gamma-secretase complex, which causes Alzheimer's disease (AD), the expression level of Prx I was firstly evaluated in an animal model for AD. NSE/hPen-2 transgenic (Tg) mice, which were used as animal model in this study, showed a high level of Pen-2 expression and accumulation of Abeta-42 peptides in the hippocampus of brain. The expression level of Prx I was significantly higher on the mRNA and protein level in the brain of this model, while not change in Prx VI expression was observed. Furthermore, to verify the effect of Prx I on the gamma-secretase components in vitro, the expression level of these components was analyzed in the Prx I transfectants. Of the components of the gamma-secretase complex, the expression of PS-2 and Pen-2 was lower in the transfectants overexpressing Prx I compared to the vector transfectants. However, the expression of APP, NCT and APH-1 did not change in Prx I transfectants. Therefore, these results suggested that the expression of Prx I may be induced by the accumulation of Abeta-42 peptides and the overexpression of Prx I in neuroblastoma cells may regulate the expression of gamma-secretase components.

The Bone Grinding and Scaffold Grafting Techniques for Guide Bone Regeneration Induce the Stress on the Rat Brain / 한국실험동물학회지

Guided bone regeneration (GBR) is a technique that a barrier membrane is placed over the bone defect to prevent the cell growth from the connective tissue and epithelium. In this study, in order to determine whether GBR technique could induce stress in rats, the standardized bone defect in rat calvaria was covered with apatitte membrane. Bone and brain tissues were collected from rats at 3 days, 2, 4, and 16 weeks post-operation, and then alteration of the new bone formation at the defects and stress-related factors were detected with histological examination and Western blot, respectively. From 4 to 16 weeks after the operation, the apatitte membrane was attached to the region of regenerated bone and encapsulated with a thick fibrous layer. Furthermore, the concentration of cortisol, a good indicator of stress, significantly increased 3 days post-operation. However, the increase at 3 days was returned to the basal level in 2 weeks. In Western blot analysis, the highest phosphorylation level of extracellular signal-regulated kinase (ERK) was observed 3 day post-operation, while those of the c-jun N-terminal kinase (JNK) and p38 were detected 4 weeks post-operation. Taken together, the results suggest that GBR technique may induce the serious stress on the brain tissue via the induction of ERK phosphorylation during 2 weeks, and that the stress responses restored in 4 week via JNK and p38 signaling pathway.

Topical Application of Selenium Can Significantly Relieve UV-induced Skin Aging in Hairless Mice / 한국실험동물학회지

Ultraviolet (UV) irradiation is an environmental factor that causes skin aging, and is also a major factor leading to cumulative alterations of skin structure, function and appearance. To investigate the effects of Selenium (Sel) on UV-induced skin aging, hairless mice were treated for 4 weeks with UV irradiation and topical application of Sel. Then, the effects of Sel were measured in the skin of these mice via histological analysis and Western blotting. According to the results of wrinkle formation analysis, the topical application of Sel induced a reduction in wrinkling formation in the damaged skin of the UV-irradiated mice. Additionally, our histological analysis demonstrated that the skin thickness in the Sel-treated group was less than in the UV-irradiated group. Furthermore, in an effort to investigate the mechanisms underlying the effects of Sel, the expression levels of matrix-metalloproteinase (MMP) and MAPK protein were assessed in both groups. The application of Sel induced a reduction in MMP-1 expression levels to the levels observed in the non-irradiated group. However, the expression level of MMP-9 was increased slightly in the Sel application group as compared with the vehicle application group. Additionally, the levels of ERK phosphorylation were increased by the application of Sel, but the levels of JNK and p38 were not altered by Sel treatment. These results suggest the possibility that Sel should be considered as a skin aging-protective and therapeutic drug candidate, which functions via the regulation of MMP expression levels.