Effects of PTEN inhibition on the regulation of Tau phosphorylation in rat cortical neuronal injury after oxygen and glucose deprivation

Abstract

Objective: This report investigated the involvement of the PTEN pathway in the regulation of Tau phosphorylation using an oxygen and glucose deprivation (OGD) model with rat cortical neurons.

Methods: Primary cortical neurons were used to establish the oxygen and glucose deprivation (OGD) model in vitro. These were randomly divided into control, OGD, bpV+OGD, As+OGD, Se+OGD and Mock treatment groups. The neuron viability was assessed by MTT, the cell apoptosis was detected using TUNEL staining. The expression of Phospho-PTEN/PTEN, Phospho-Tau/Tau, Phospho-Akt/Akt and Phospho-GSK-3β/GSK-3β were detected by Western blotting.

Results: OGD induced Tau phosphorylation through PTEN and glycogen synthase kinase-3β (GSK-3β) activation, together with a decrease in AKT activity. Pre-treatment with bpv, a potent PTEN inhibitor, and PTEN antisense nucleotides decreased PTEN and GSK-3β activity and caused alterations in Tau phosphorylation. Neuronal apoptosis was also reduced.

Conclusions: The PTEN/Akt/GSK-3β/Tau pathway is involved in the regulation of neuronal injury, providing a novel route for protecting neurons following neonatal HI.

Keywords:

• Neuron
• hypoxia-ischaemia
• oxygen and glucose deprivation
• signalling pathway
• PTEN
• tau
• Akt

Declaration of interest

The authors report no conflicts of interest. This work was supported by the National Science Foundation of China (No. 81300528 to Jing Zhao), Grants from Education Bureau of Sichuan province (14ZA0196), Grants from Health Bureau of Sichuan province (130339) and Grants from North Sichuan Medical College (CBY12-A-QN21).