ObjectiveTo explore the protective effect of glucocorticoid-induced transcription factor 1 （GLCCI1） on cognitive dysfunction in diabetic mice and its mechanism. MethodsTwenty-four C57BL/6J mice were randomly divided into 4 groups， namely Control， DM， DM+AAV-Glcci1， and DM+AAV-NC. The Control group was intraperitoneally injected with saline， while the other groups were all injected with streptozotocin （STZ）. Two weeks after successful modeling， the DM+AAV-Glcci1 group was brain stereotactic injected with Glcci1 overexpressing adeno-associated virus， and the DM+AAV-NC group was stereoscopically injected with the control virus. After 12 weeks， the Morris water maze test was used to evaluate the learning and memory abilities of mice in each group. Subsequently， the localized expression of GLCCI1 in the hippocampus were determined by immunofluorescence and immunohistochemistry experiments. The myelin morphology in the hippocampus was observed by LFB staining， the neuronal morphology was observed by Nissl staining， and the myelin-related proteins MBP and CNPase were stained by immunohistochemistry. Molecular docking was used to predict the interaction between GLCCI1 and HSPA5. The expression of endoplasmic reticulum stress-related proteins was detected by Western blot. ResultsThe results of the behavioral experiment showed that compared with the mice in the Control group， DM mice exhibited obvious cognitive dysfunction behaviors （P＜0.000 1）， and the learning and memory abilities of mice improved after overexpression of Glcci1 （P=0.000 7）. The results of immunofluorescence and immunohistochemistry showed that GLCCI1 was expressed in hippocampal neuron cells. Compared with Control mice， the expression level of GLCCI1 in DM mice was significantly downregulated （P＜0.000 1）. The molecular docking results revealed that GLCCI1 interacts with HSPA5. The Western blot results indicated that， compared with the Control group， the expression levels of endoplasmic reticulum stress-related proteins HSPA5 （P＜0.000 1）， ATF4 （P＜0.000 1）， ATF6 （P=0.001 1）， and p-ELF2α/elF2α （P=0.000 1） in the DM group were significantly increased； Compared with the DM group， the expression of the corresponding protein HSPA5 （P＜0.000 1）， ATF4 （P＜0.000 1）， ATF6 （P=0.000 2）， and p-ELF2α/elF2α （P=0.000 1） was significantly down-regulated after overexpression of Glcci1. LFB staining showed that compared with the Control group， the myelin integrity of DM mice decreased significantly （P=0.010 3）， the expressions of myelin-related proteins MBP and CNPase decreased significantly （P=0.000 4， P=0.000 2）， and Nissl staining observed disordered neuronal arrangement. Compared with the mice in the DM group， the myelin integrity in the hippocampal region significantly increased after overexpression of Glcci1 （P=0.000 3）， the expressions of myelin-related proteins MBP and CNPase significantly increased （P=0.001 4， P=0.000 1）， and the ordered arrangement of neurons was observed by Nissl staining. ConclusionThe down-regulation of GLCCI1 expression in hippocampal neurons promotes demyelination of hippocampal neurons and thereby induces diabetic cognitive dysfunction. The specific mechanism may be related to endoplasmic reticulum stress.

Objective To study the relationship between the changes of TRIM16 in hippocampus of type 2 diabetic rats induced by streptozotocin (STZ) and cognitive dysfunction and apoptosis of hippocampal cells.Methods The male Sprague-Dawley (SD) rats of 8 weeks old were randomly divided into diabetic group (DM group) (n=25) and normal control group (NC group) (n=15).NC group were given normal feed, DM rats were fed with high glucose and high fat diet,followed by low dose of STZ (25 mg/kg, intraperitoneal injection), induced compensatory secretion of insulin, five days after the detection of tail vein blood glucose>16.7 mmol/L, and established the STZ.Meanwhile, citric acid buffer was injected to rats in group as control.After successful modeling, the rats in the two groups were fed with 17 weeks.Morris water maze test was used to detect the cognitive function of the two groups of rats.The protein expression of TRIM16, Bax and Bcl-2 protein in fresh hippocampus tissue of DM group and NC group rats was detected using western blotting.Rats in DM group and NC group were perfused with brain, and the hippocampal tissues were stained with immunohistochemistry.TUNEL method was used to detect the apoptosis of hippocampus cells.ResultsCompared with NC group, morris water maze test showed that the escape latency of rats in DM group is longer than NC group, staying at the original platform quadrant time in DM group is less than the NC group.TUNEL assay showed that after injection of 17 weeks, hippocampal CA1 pyramidal cells in type 2 diabetic rats appeared obvious apoptosis, positive neurons in the nuclei were brown, karyopyknosis anachromasis, while control group of neurons in the nucleus without brown coloring.Compared with the NC group, hippocampus immunohistochemistry results showed that the protein of TRIM16 in hippocampus CA1 region of type 2 diabetic rats was increased, cytoplasm brown, coarse granular.Compared with the NC group, the expression of Bcl-2 had no obvious change in hippocampus of type 2 diabetic rats at 17 weeks, while the expression of TRIM16, Bax and the ratio of Bax/Bcl-2 was significantly increased (P<0.05).Conclusion The protein expression of TRIM16 using immunohistochemical and Western blotting in hippocampus of diabetic rats induced by STZ was increased.There is apoptosis in hippocampus of diabetic rats induced by STZ, the expression of Bcl-2 was not significantly changed, the expression of Bax and the ratio of Bax/Bcl-2 were significantly increased.TRIM16 is involved in diabetic cognitive dysfunction by promoting apoptosis of diabetic rat hippocampus.

OBJECTIVE To clarify the influence factors of hearing impairment in mice caused by lack of folic acid and the mechanism.METHODS Mice were randomly divided into 2 groups,fed with no folic acid diet and normal diet for 10 weeks.Hearing was tested by ABR.Serum homocysteine,folic acid were detected.Immune imprint method was used to analyze the expression of related protein.Cochlear tissue was tested by histological method to observe morphological changes.At the same time using the TUNEL method was used to analyse the cochlear tissue cell apoptosis.RESULTS Analysis showed that serum folate levels in mice fed without folic acid diet dropped than that of the normal group,while homocysteine levels elevated.Through the brain stem auditory records and cochlear cell apoptosis of mice severe hearing loss was found in folate deficiency group.Western blot detection showed enzyme catalysis homocysteine products increased by 50％ in folate deficiency group than that of the normal diet group.CONCLUSION The high homocysteine levels,and folate deficiency can cause hearing loss in mice and are related with the inner ear homocysteine metabolic disorders.

Objective To explore protective effects of panaxtrial saponins (PTS) on cognition and memory of diabetic rats and to reveal its mechanism by which might involve regulating activity of astrocytes. Methods SD rats (n=24) were ran?domly assigned into control, diabetic and PTS-treated groups (n=8 in each group). Rat diabetic model was induced through streptozotocin injection intraperitoneally. Rats in control group were native rats, and rats in PTS-treated group were diabetic rats that were administered with PTS. Body weight and blood glucose were monitored through the experiments. Three months later, state of cognition was examined by methods of water maze. Hippocampal astrocyte morphology were detected by immu?nohistochemistry, and the expression of glial cell line-derived neurotrophic factor (GDNF) and glial fibrillary acidic protein (GFAP) in hippocampus were revealed by Western blot. Results Compared with control group, diabetic group showed cog?nitive dysfunction, atrophic astrocyte soma, shrinked astrocyte processes, and down-regulation of hippocampal GFAP and GDNF (P<0.05). Compared with diabetic group, PTS-treated group exhibited improved cognition and morphology of hippo?campal astrocyte, and reversed expression of GFAP and GDNF in diabetic hippocampus (P<0.05). Conclusion PTS re?versed astrocytic reactivity as well as expression of GDNF and GFAP in diabetic hippocampus and ameliorated diabetic cog?nitive dysfunction.