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Depotentiation of Long-Term Potentiation Is Associated with Epitope-Specific Tau Hyper-/Hypophosphorylation in the Hippocampus of Adult Rats

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Abstract

It is well-known that some kinases which are involved in the induction of synaptic plasticity probably modulate tau phosphorylation. However, how depression of potentiated synaptic strength contributes to tau phosphorylation is unclear because of the lack of experiments in which depotentiation of LTP was induced. Field excitatory postsynaptic potential (fEPSP) and population spike (PS) were recorded from the dentate gyrus in response to the perforant pathway stimulation. To induce LTP, high-frequency stimulation (HFS) was used, while, for depotentiation of LTP, low-frequency stimulation (LFS) consisting of 900 pulses at 1 Hz was applied 5 min after tetanization. In some experiments, a neutral protocol at 0.033 Hz was applied throughout the experiment without any induction of synaptic plasticity. One-hertz depotentiation protocol was able to decrease fEPSP slope which was previously increased by HFS, whereas no significant change in fEPSP slope and PS amplitude was observed in neutral protocol experiments. Relative to saline infusion, LTP was lower in magnitude and was more reversed by subsequent LFS in the presence of ERK1/2 inhibitor. Western blot experiments indicated that tau protein was hyperphosphorylated at ser416 epitope but rather hypophosphorylated at thr231 epitope in the whole hippocampus upon depotentiation of LTP. These changes concomitantly occurred with a notable increase in the levels of total tau and in the levels of phosphorylated form of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). ERK1/2 inhibition resulted in a decrease in phosphorylation of tau at p416Tau when ERK1/2 was inhibited. These findings indicate that some forms of long-term plastic changes might be related with epitope-specific tau phosphorylation and ERK1/2 activation in the hippocampus. Therefore, we emphasize that tau may be crucial for physiological learning as well as Alzheimer’s disease pathology.

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Funding

Support was from the Scientific and Technological Research Council of Turkey (TUBITAK) for providing the Student Laboratory Experience Grant. This research was financially supported by Erciyes University Research Found grant number TDK-2016-6628 to C.S.

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  1. Department of Physiology, Medical School of Erciyes University, Kayseri, Turkey

    Ercan Babür, Burak Tan, Sumeyra Delibaş, Marwa Yousef, Nurcan Dursun & Cem Süer

  2. Department of Physiology Faculty of Medicine, Erciyes University, 38039, Kayseri, Turkey

    Cem Süer

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  1. Ercan Babür
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Table 1

Primary antibodies used for Western blot (WB) analysis (DOCX 13 kb)

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Babür, E., Tan, B., Delibaş, S. et al. Depotentiation of Long-Term Potentiation Is Associated with Epitope-Specific Tau Hyper-/Hypophosphorylation in the Hippocampus of Adult Rats. J Mol Neurosci 67, 193–203 (2019). https://doi.org/10.1007/s12031-018-1224-x

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