Phosphorylation of Tau protein correlates with changes in hippocampal theta oscillations and reduces hippocampal excitability in Alzheimer's model.

TitlePhosphorylation of Tau protein correlates with changes in hippocampal theta oscillations and reduces hippocampal excitability in Alzheimer's model.
Publication TypeJournal Article
Year of Publication2018
AuthorsMondragon-Rodriguez S, Salas-Gallardo A, González-Pereyra P, Macías M, Ordaz B, Peña-Ortega F, Aguilar-Vázquez A, Orta-Salazar E, Díaz-Cintra S, Perry G, Williams S
JournalJ Biol Chem
Volume293
Issue22
Pagination8462-8472
Date Published2018 Jun 01
ISSN1083-351X
Abstract

Tau hyperphosphorylation at several sites, including those close to the microtubule domain region (MDr), is considered a key pathological event in the development of Alzheimer's disease (AD). Recent studies indicate that at the very early stage of this disease, increased phosphorylation in Tau's MDr domain correlates with reduced levels of neuronal excitability. Mechanistically, we show that pyramidal neurons and some parvalbumin-positive interneurons in 1-month-old triple-transgenic AD mice accumulate hyperphosphorylated Tau protein and that this accumulation correlates with changes in theta oscillations in hippocampal neurons. Pyramidal neurons from young triple-transgenic AD mice exhibited less spike accommodation and power increase in subthreshold membrane oscillations. Furthermore, triple-transgenic AD mice challenged with the potassium channel blocker 4-aminopyridine had reduced theta amplitude compared with 4-aminopyridine-treated control mice and, unlike these controls, displayed no seizure-like activity after this challenge. Collectively, our results provide new insights into AD pathogenesis and suggest that increases in Tau phosphorylation at the initial stages of the disease represent neuronal responses that compensate for brain circuit overexcitation.

DOI10.1074/jbc.RA117.001187
Alternate JournalJ. Biol. Chem.
PubMed ID29632073
PubMed Central IDPMC5986208
Grant ListG12 MD007591 / MD / NIMHD NIH HHS / United States

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