Effects of intracranial co-infusion of Aβ_(1-42) and thiorphan on Macaca Rhesus hippocampal formation / 中国药理学通报

ABSTRACT

Aim To observe the change of amyloid, acetylcholine transferase and glial fibrillary acidic protein expression in Macaca Rhesus hippocampal after infused the Aβ_(1-42) and thiorphan and explore the possibility of the establishment of Macaca Rhsus AD model in brain.Method The Rhesus monkeys were anesthetized (im), the skull was exposed by a midline scalp incision, and oriented craniotomy was performed on left side by dental drill.First, neprilysin in cerebral cortex and basal nucleus was consumed by infusion thiorphan. Then cerebral cortex and basal nucleus were slowly infused with fibrilla Aβ_(1-42). Finally, the cannula for thiorphan infusion was implanted into the basal nucleus.Miniosmotic pump (Alzet MODEL 2ML4,) was subcutaneously fixed by bio gel 454 on the calvaria (Loctite Co. Ltd,USA) according to the manufacturer's instructions.After 50 days' survival, animals were deep anesthetized with ketamine and sacrificed. The pathological changes were observed by HE staining and immunostaining in monkey brains.Result Neuronal loss and a proliferation of microglia were detected in hippocampal formation by HE staining.Immuno-staining showed Aβ_(1-42),ChAT and GFAP positive cells density were 0.59±0.05,0.21±0.04 and 0.19±0.04 separately.Compared with control group, the density in experimental groups showed distinct difference in statistic analysis (P<0.01).Conclusion The same pathological change was detected in the thioaphan and Aβ_(1-42) infusion in Macaca Rhesus hippocampal formation as what was found in AD patients.