期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 293, 期 22, 页码 8462-8472出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA117.001187
关键词
Alzheimer disease; Tau protein (Tau); tauopathy; biomarker; genetics; compensatory mechanism; epileptiform activity; hyperphosphorylation; Tau; theta activity
资金
- CONACYT [612271, 770620, 269021, 117-235789]
- DGAPA-UNAM [IN202018]
- Fundacion Marcos Moshinsky
- National Institute of Minority Health and Health Disparities from the National Institutes of Health [G12MD007591]
- Semmes Foundation
- National Institute on Minority Health and Health Disparities [G12MD007591] Funding Source: NIH RePORTER
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据