Effect of Xixin decoction on phosphorylation toxicity at specific sites of tau protein in brains of rats with sporadic Alzheimer disease

OBJECTIVE: To explore the mechanism of action of Xixin decoction(XXD) for the prevention and treatment of sporadic Alzheimer disease(SAD) by investigating the effects of XXD on the phosphorylation of Thr231 and Ser422 sites of tau protein. METHODS: Specific pathogen-free(SPF) male Sprague-Dawley(SD) rats with SAD were randomly divided into six groups: sham-operated, model(intracerebroventricular injection of Streptozotocin, ICV-STZ), donepezil(0.92 mg/kg), XXD low-dose(7.61 g/kg-1 ·d-1), moderate-dose(15.21 g/kg-1 ·d-1), and high-dose(30.42 g/kg-1 ·d-1). Immunohistochemistry and western immunoblotting were used to detect the phosphorylation at Thr231 and Ser422 sites of tau protein. RESULTS: XXD different dose groups decreased to varying degrees the expression of phosphorylated tau at P-Thr231 and P-Ser422 sites in the hippocam-pus of SAD rats. No significant difference was found between the donepezil and model group. CONCLUSION: XXD may prevent SAD pathological progress by inhibiting hyperphosphorylation at the key sites of tau proteins.

Knock-down of postsynaptic density protein 95 expression by antisense oligonucleotides protects against apoptosis-like cell death induced by oxygen-glucose deprivation in vitro

Objective Postsynaptic density protein 95 （PSD-95） plays important roles in the regulation of glutamate signaling, such as that of N-methyl-D-aspartate receptors （NMDARs）. In this study, the functional roles of PSD-95 in tyrosine phosphorylafion of NMDAR subunit 2A （NR2A） and in apoptosis-like cell death induced by oxygen-glucose de- privation （OGD） in cultured rat cortical neurons were investigated. Methods We used immunoprecipitation and immuno- blotting to detect PSD-95 protein level, tyrosine phosphorylation level of NR2A, and the interaction between PSD-95 and NR2A or Src. Apoptosis-like cells were observed by 4,6-diamidino-2-phenylindole staining. Results Tyrosine phospho- rylation of NR2A and apoptosis-like cell death were increased after recovery following 60-min OGD. The increases were attenuated by pretreatment with antisense oligonucleotides against PSD-95 before OGD, but not by missense oligonucle- otides or vehicle. PSD-95 antisense oligonucleotides also inhibited the increased interaction between PSD-95 and NR2A or Src, while NR2A expression did not change under this condition. Conclusion PSD-95 may be involved in regulating NR2A tyrosine phosphorylation by Src kinase. Inhibition of PSD-95 expression can be neuroprotective against apoptosis- like cell death after recovery from OGD.