The molecular mechanisms regulating N-methyl-d-aspartate (NMDA) receptor-dependent synaptic plasticity are complex, and the contribution of Tau protein in the physiological process is not fully understood. Herein, we investigated whether the blockade of NMDA receptor activation might change Tau phosphorylation during long-term potentiation (LTP) and long-term depression (LTD) via contribution of GSK3β as a major Tau kinase. For this, we recorded two components (synaptic and population spike components) of hippocampal field potential, which is evoked by the stimulation of the perforant pathway with high- and low-frequency stimulation (HFS and LFS). We found under a 20-µl volume of D-AP5 infusion lasting 1 h that,HFS caused significant synaptic depression, whereas LFS induced a synaptic potentiation. Both the HFS and LFS protocols resulted in a significant increase in population spike component but were characterized by a slow increase in amplitude that occurred with the LFS. D-AP5 attenuated HFS-induced population spike potentiation, but augmented LFS-induced population spike potentiation. The enzymatic activity of GSK-3β was decreased by D-AP5 infusion in the hippocampus, indicating that NMDA receptor activity modulates the enzymatic activity of GSK-3β. In addition, NMDA receptor blockade reduced tau expression and phosphorylation of tau at Ser416 residue, but not Thr231 residue. These findings confirm previous studies that D-AP5 applied to the DG in vivo blocks HFS-induced LTP, but we further also showed that the same dose of D-AP5 resulted in a slowly rising LFS-induced LTP and HFS-induced LTD. The formation of such an LTP, together with reduced enzymatic activity of GSK-3β and tau phosphorylation at Ser416 epitope, can make it a candidate mechanism for prevention of taupathies.
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This study was funded by The Research Foundation of Erciyes University of Turkey (Grant number: TDK-2016–6628). Authors Burak Tan, Ezgi Aslan Gülpınar, Nurcan Dursun, Cem Süer were received research Grants from Erciyes University, School of Medicine, Department of Physiology.
Conflict of interest
Authors Burak Tan declares that he has no conflict of interest. Author Ezgi Aslan Gülpınar declares that she has no conflict of interest. Author Nurcan Dursun declares that she has no conflict of interest. Author Cem Süer declares that he has no conflict of interest.
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Communicated by Sreedharan Sajikumar.
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Tan, B., Aslan-Gülpınar, E., Dursun, N. et al. N-methyl-d-aspartate receptor blockade reduces plasticity-related tau expression and phosphorylation of tau at Ser416 residue but not Thr231 residue. Exp Brain Res 239, 1627–1637 (2021). https://doi.org/10.1007/s00221-021-06090-z
- Synaptic plasticity
- Long-term potentiation
- Long-term depression