Tanshinone IIA Ameliorates Spatial Learning and Memory Deficits by Inhibiting the Activity of ERK and GSK-3β.
J Geriatr Psychiatry Neurol. 2019 Mar 18:891988719837373. Epub 2019 Mar 18. PMID: 30885037
BACKGROUND:: Alzheimer disease (AD) is the most common type of dementia which is becoming a primary problem in the present society, but it lacks effective treatment methods and means of AD. Tanshinone IIA (Tan IIA) has been reported to have neuroprotective effects to restrain the Aβ-mediated apoptosis. However, few studies try to understand how Aβaffects hyperphosphorylation of tau and how Tan IIA regulates this process at the molecular level.
METHODS:: Fifty male Sprague-Dawley rats were randomly divided into 5 groups and infused through the lateral ventricle with Aβexcept the control group. Then the rats were treated with Tan IIA through intragastric administration for 4 weeks. After the ability of learning and memory being measured, histomorphological examination and Western blot were used to detect the possible mechanism in the AD-associated model rats.
RESULTS:: We observed that Aβinfusion could induce spatial learning and memory deficits in rats. Simultaneously, Aβalso could reduce the neuron in cornu ammonis 1 and dentate gyrus of hippocampus, as well as increase the levels of cleaved caspase 3, hyperphosphorylated tau at the sites Ser396, Ser404, and Thr205 with enhancing staining of black granules in brain. We also found that Aβcould increase the activity of extracellular signal-regulated protein kinase (ERK) and glycogen synthase kinase-3β (GSK-3β). Meanwhile, these phenomena could be ameliorated when Tan IIA was used.
CONCLUSION:: We concluded that Tan IIA might have neuroprotective effect and improving learning and memory ability to be a viable candidate in AD therapy with mechanisms involving the ERK and GSK-3β signal pathway.