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J Geriatr Psychiatry Neurol. 2019 May;32(3):152-163. doi: 10.1177/0891988719837373. Epub 2019 Mar 18.

Tanshinone IIA Ameliorates Spatial Learning and Memory Deficits by Inhibiting the Activity of ERK and GSK-3β.

Author information

1
1 Cell Molecular Biology Laboratory of Basic Medical College, Hubei University of Chinese Medicine, Wuhan, China.
2
2 Hubei Research Institute of Geriatrics, Collaborative Innovation Center of Hubei Province, Hubei University of Chinese Medicine, Wuhan, China.
3
3 Department of Pharmacology, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.

Abstract

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 Aβ25 -35-mediated apoptosis. However, few studies try to understand how Aβ1-42 affects 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 Aβ1-42 except 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 Aβ1-42 infusion could induce spatial learning and memory deficits in rats. Simultaneously, Aβ1-42 also 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 Aβ1-42 could 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.

KEYWORDS:

Alzheimer disease; extracellular signal-regulated protein kinase; glycogen synthase kinase-3β; hyperphosphorylated tau protein; spatial learning and memory deficits; tanshinones IIA

PMID:
30885037
DOI:
10.1177/0891988719837373

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