[Verification of a sporadic Alzheimer disease model in SORL1 gene knockout mice].

OBJECTIVE: To compare the behavioral and pathological features of SORL1 gene knockout mice with those of normal mice and APP/PSE1 mice to verify the feasibility of using SORL1 knockout mice as a model of sporadic Alzheimer disease. METHODS: SORL1 gene of fertilized mouse eggs were edited using Crispr/Case9 technique. SORL1-/- mice were screened and identified by detecting the DNA sequence, and Western blotting was used to detect the expression of SORL1. SORL1-/- mice, control mice and APP/PSE1 mice all underwent Morris water maze test to assess their learning and memory abilities with positioning navigation and space exploration experiments. The expression of APP and Aß in the brain of the mice was detected using immunohistochemistry and Western blotting, respectively. RESULTS: DNA sequencing showed CAAT deletion in SORL1 gene in two chromosomes of SORL1-/- mice, and the control mice had intact SORL1 gene without the deletion; Western blotting did not detect the expression of the SORL1 in the brain of SORL1-/- mice. Morris water maze test showed that in positioning navigation experiment, the average avoidance latency was similar between SORL1-/- mice and APP/PSE1 mice (P>0.05) but increased significantly in both mice as compared with the control group (P<0.05); similar results were obtained in the space exploration experiment. Immunohistochemistry and Western blotting revealed significantly increased APP and Aß expression in the brain tissue of both SORL1-/- mice and APP/PSE1 mice compared with the control mice without significant differences between the two transgenic mice. CONCLUSION: SORL1-/- mice exhibit similar behavioral and pathological changes with APP/PSE1 mice and can be used as a model of sporadic Alzheimer's disease.

[Protective effect of butylphthalide in a cell model of Alzheimer's disease induced by Aß25-35 in Neuro 2a cells].

OBJECTIVE: To study the protective effect of butylphthalide in a cell model of Alzheimer's disease(AD) induced by Aß25-35 in Neuro 2a (N2a) cells. METHODS: N2a cells were divided into AD group, butylphthalide (NBP) group and control group. AD cell model was established by adding 20 µmol/L Aß25-35 to cultured N2a cells. The cells in NBP group were treated with 0.1, 1, 10, or 100 µmol/L NBP 4 h prior to treatment with 20 µmol/L Aß25-35. The cell viability were determined by MTT assay, the cell apoptotic rate were detected by AnnexinV-FITC flow cytometry, and the cell morphological changes were observed under inverted phase contrast microscope. The expression of TNF-α and IL-1ß mRNA were determined by qRT-PCR. RESULTS: Compared with those in the control group, the number of adherent cells was significantly decreased, neurite structures were reduced, and the cell viability was decreased, while the apoptotic rate and expressions of TNF-α and IL-1ß mRNA were increased in AD group (P<0.05). Compared with that in AD group, the number of adherent cells was increased in NBP group and the cell morphology was similar to the normal control cells. The cell viability of N2a cells was increased in NBP group with decreased apoptotic rate and expression of TNF-αand IL-1ß mRNA (P<0.05). CONCLUSION: Butylphthalide can protect against AD in the cell model induced by Aß25-35 possibly by inhibiting the expression of inflammatory cytokines.

[Research progress of depression and the application of esketamine].

OBJECTIVE: The pathogenesis and etiology of still remain unknown. Current evidence suggests that the occurrence of depression may be related to a reduced secretion of neurotransmitters, neuronal apoptosis, inflammation, intestinal flora and other factors. Although the commonly used antidepressants such as SSRIs, SNRIs, NaSSA, and SARIs produce some therapeutic effects, they fail to relieve the full spectrum of the symptoms of depression. In recent years, esketamine was found to produce a potent and a long-lasting antidepressant effect by acting on the NMDA receptors. Herein the authors review the progress in the study of the pathogenesis and drug therapies of depression, the efficacy of esketamine treatment and the underlying mechanism, and the prospect of esketamine treatment. Currently the mechanism of the antidepressant effect of esketamine remains indeterminate and its clinical application is limited, but its effect in rapidly alleviating the symptoms of depression suggests its bright prospect for clinical applications.