Affiliations: [a] Department of Pathophysiology, Key Laboratory of Neurological Disease of Education Ministry of China, Tongji Medical College, Huazhong University of Science and Technical, Wuhan, China | [b] Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technical, Wuhan, China
Correspondence:
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Corresponding author: Dr. Qing Tian, Department of Pathophysiology, Key Laboratory of Neurological Disease Education Ministry of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Tel.: +86 27 83692625; Fax: +86 27 83693883; E-mail: [email protected] and [email protected].
Note: [] Communicated by Xiongwei Zhu
Abstract: To explore the role of protein kinase A (PKA) in regulating tau phosphorylation and spatial memory, we injected forskolin, an activator of PKA, at different concentrations into the rat brains. We found that forskolin at concentrations up to 80 μM enhanced tau phosphorylation and was associated with prominent spatial memory impairment. Higher concentrations of forskolin, up to 200 μM, were associated with reduced phosphorylation levels of tau and no memory deficits. Forskolin elevated cAMP and activated PKA in a dose-dependent manner. When infused at 200 μM, forskolin also resulted in the activation and overexpression of protein phosphatase-2A (PP-2A) and attenuated the okadaic acid-induced PP-2A inhibition. These data suggest that the upregulation of PKA by forskolin to a certain level may activate PP-2A but that the latter can ameliorate the PKA-induced tau phosphorylation and memory impairment in the rats.
Keywords: Alzheimer's disease, forskolin, phosphorylation, protein kinase A, protein phosphatase-2A, tau
