Long-term Depression-related Tau Phosphorylation is Enhanced by Methylene Blue in Healthy Rat Hippocampus

Overview

Journal Pharmacol Rep

Specialty Pharmacology

Date 2021 Apr 2

PMID 33797746

Citations 1

Authors

Cem Suer

Nurbanu Yildiz

Ozlem Barutcu

Burak Tan

Nurcan Dursun

Affiliations

Soon will be listed here.

Abstract

Background: The present study examined whether inhibition of guanylate cyclase (GC) is associated with the plasticity-related microtubule-stabilizing protein tau phosphorylation in the dentate gyrus (DG) of hippocampal formation.

Methods: To address this issue, methylene blue (MB 50 μM) or saline was infused into the DG starting from the induction of long-term potentiation (LTP) or depression (LTD) for 1 h. Then, protein phosphatase 1 alpha (PP1α), glycogen synthase kinase 3 beta (GSK3β), and tau total and phosphorylated protein levels were measured in these hippocampi using western blotting. LTP and LTD were induced by application of high- and low-frequency stimulation protocols (HFS and LFS), respectively. 5-min averages of the excitatory postsynaptic potential (EPSP) slopes and population spike amplitudes at the end of recording were averaged to measure the magnitude of LTP or LTD.

Results: Low-frequency stimulation protocols was unable to phosphorylate thr and threpitopes of tau, but possessed kinase activity similar to the HFS in phosphorylation of ser and ser epitopes. MB infusion during LTD induction attenuated LTD, prevented EPSP/spike dissociation and increased tau phosphorylation at ser and ser epitopes, without changing tau phosphorylation at thr and thr epitopes. Neither LTP nor LTP-related tau phosphorylation state was changed by MB infusion.

Conclusion: Although MB can benefit to stabilize the balance between LTP and LTD, and to fix the increased spike wave discharges, it might trigger deregulation of tau phosphorylation, leading to the development of Alzheimer's disease by a mechanism that goes awry during induction of LTD. Thereby detailed studies to reveal more precise evidence for the use of MB in this disease are needed.

Citing Articles

Do tau-synaptic long-term depression interactions in the hippocampus play a pivotal role in the progression of Alzheimer's disease?.

Hu Z, Ondrejcak T, Yu P, Zhang Y, Yang Y, Klyubin I Neural Regen Res. 2022; 18(6):1213-1219.

PMID: 36453396 PMC: 9838152. DOI: 10.4103/1673-5374.360166.

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