Presence of White Matter Lesions Associated with Diabetes-Associated Cognitive Decline in Male Rat Models of Pre-Type 2 Diabetes.

BACKGROUND The aim of this study was to determine the association between white matter lesions (WML) and diabetes-associated cognitive decline (DACD) in rat models of type 2 diabetes (T2DM). MATERIAL AND METHODS Sixty Sprague-Dawley male rats were divided into 4 groups: control, control+metformin, T2DM, and T2DM+metformin groups. The T2DM groups were fed a diet high in fat and glucose to induce impaired glucose tolerance (IGT) and then were injected with streptozotocin to induce T2DM. The Morris water maze test was used to evaluate cognitive function. Brain diffusion tensor imaging scans were performed for WML. The expression of myelin basic protein (MBP), oligodendrocyte transcription factor 1 (OLIG1), and OLIG2 (markers of brain damage and repair) was determined using immunofluorescence. After IGT, the fractional anisotropy (FA) values of the right thalamus area were significantly lower in both T2DM groups compared with controls. RESULTS Eight weeks after streptozotocin injection, the FA values of the thalamus were lower in the T2DM (bilateral thalamus) group and T2DM+metformin (left thalamus) group than in controls, while the FA values in the left thalamus area were lower in the T2DM+metformin group than in the control and control+metformin groups. The maze escape latency was longer and the number of rats passing through the platform was smaller in the T2DM and T2DM+metformin groups than in the control group. MBP levels were lower and OLIG1 and OLIG2 levels were higher in both T2DM groups than in controls. CONCLUSIONS WML is associated with DACD and appears before the onset of T2DM and signs of DACD and plays a role in diabetes-associated cognitive decline. Metformin reduces WMLs but does not rescue cognitive dysfunction.

Effect of selenium on fluoride-induced changes in synaptic plasticity in rat hippocampus.

This study was conducted to further explore the effect of selenium on fluoride-induced changes in the synaptic plasticity in rat hippocampus. Animals were randomly divided into control group, F group (sodium fluoride: 50 mg/L), three Se groups (sodium selenite: 0.375, 0.75, and 1.5 mg/L), and three F+Se groups (sodium fluoride: 50 mg/L; sodium selenite:0.375, 0.75, and 1.5 mg/L) and subjected to an exposure time of 6 months. The changes in synaptic plasticity in rat hippocampus were observed by electron microscopy. Compared with the fluoride group, the length of the synaptic active zone and the thickness of the postsynaptic density (PSD) increased significantly, whereas the width of the synaptic cleft decreased with high significance in the F+Se (0.75 mg/L) group. Moreover, the nitric oxide synthase activity and the nitric oxide content in the hippocampus decreased significantly in the F+Se (0.75 and 1.5 mg/L) groups. Furthermore, reverse transcriptase polymerase chain reaction and Western blot analyses showed that postsynaptic density-93 (PSD-93) expression in the hippocampus was increased significantly, whereas postsynaptic density-95 (PSD-95) expression decreased significantly in the fluoride group compared with the control group. The PSD-93 expression was inhibited in the three F+Se groups, whereas the opposite result was observed in PSD-95 expression. Based on the results, the optimal selenium dosage range that can antagonize the neurotoxicity of fluorosis is from 0.75 to 1.5 mg/L. The changes in PSD-93 expression may be the key factor to fluoride-induced central nervous toxicity and the effect of selenium intervention.

Effects of selenium intervention on chronic fluorosis-induced renal cell apoptosis in rats.

This study aims to explore the effect of selenium in fluoride-induced renal cell apoptosis in rats and determine the optimal level of selenium in drinking water to prevent fluorosis. Experimental animals were divided into a control group, a sodium fluoride-treated group (NaF, 50 mg/L), three sodium selenite-treated groups (Na2SeO3, 0.375, 0.75, and 1.5 mg/L), and three selenium + NaF-treated groups (Na2SeO3, 0.375, 0.75, and 1.5 mg/L; NaF, 50 mg/L). Ultrastructural changes in the kidney tissues of each group were observed by transmission electron microscopy. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and the expressions of Bcl-2 and Bax proteins were detected by immunohistochemical methods. The expressions of Bcl-2 and Bax mRNA were detected by reverse transcription-polymerase chain reaction. The results showed that Bcl-2, Bax, and Bax/Bcl-2 protein expressions in the fluoride and high selenium groups were highly elevated compared with the control group (P < 0.01). Bax expression in the low selenium group and Bcl-2, Bax, and Bax/Bcl-2 protein expressions in the moderate selenium groups were observably elevated (P < 0.05). Bax and Bax/Bcl-2 expressions in the fluoride group and Bax mRNA expression in the high selenium group were highly elevated (P < 0.01). Bax/Bcl-2 mRNA expression in the high selenium group was also highly elevated (P < 0.05). Compared with the fluoride group, the group treated with low selenium has Bax protein expression that was observably reduced (P < 0.05); the group treated with moderate selenium has Bcl-2 protein expression that was observably elevated (P < 0.05), Bax protein expression that was highly reduced (P < 0.01), and Bax/Bcl-2 protein expression that was observably reduced (P < 0.05); the group treated with high selenium has Bcl-2 protein expression that was highly elevated (P < 0.01), Bax protein expression that was highly elevated (P < 0.01), and Bax/Bcl-2 protein expression that was highly reduced (P < 0.01); the groups treated with moderate selenium and high selenium have Bax mRNA expression that was highly reduced (P < 0.01), and the groups treated with high selenium have Bax/Bcl-2 mRNA expression that was observably reduced (P < 0.05). Selenium may inhibit the apoptosis of renal cells in fluorosis rats by regulating the expressions of Bcl-2 and Bax. The optimal dose of Na2SeO3 to protect against fluoride-induced renal cell apoptosis was determined to be 1.5 mg/L.