Improved long-term potentiation and memory in young tau-P301L transgenic mice before onset of hyperphosphorylation and tauopathy

被引:133
作者
Boekhoorn, K
Terwel, D
Biemans, B
Borghgraef, P
Wiegert, O
Ramakers, GJA
de Vos, K
Krugers, H
Tomiyama, T
Mori, H
Joels, M
van Leuven, F
Lucassen, PJ
机构
[1] Katholieke Univ Leuven, Dept Human Genet, Expt Genet Grp, B-3000 Louvain, Belgium
[2] Univ Amsterdam, Ctr Neurosci, Swammerdam Inst Life Sci, NL-1098 SM Amsterdam, Netherlands
[3] Netherlands Inst Brain Res, NL-1105 AZ Amsterdam, Netherlands
[4] Sch Med, Dept Neurosci, Abeno Ku, Osaka 5458585, Japan
关键词
LTP; neurodegeneration; memory; dendate gyrus; neurogenesis; Golgi impregnation;
D O I
10.1523/JNEUROSCI.5425-05.2006
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The microtubule binding protein tau is implicated in neurodegenerative tauopathies, including frontotemporal dementia (FTD) with Parkinsonism caused by diverse mutations in the tau gene. Hyperphosphorylation of tau is considered crucial in the age-related formation of neurofibrillary tangles (NFTs) correlating well with neurotoxicity and cognitive defects. Transgenic mice expressing FTD mutant tau-P301L recapitulate the human pathology with progressive neuronal impairment and accumulation of NFT. Here, we studied tau-P301L mice for parameters of learning and memory at a young age, before hyperphosphorylation and tauopathy were apparent. Unexpectedly, in young tau-P301L mice, increased long-term potentiation in the dentate gyrus was observed in parallel with improved cognitive performance in object recognition tests. Neither tau phosphorylation, neurogenesis, nor other morphological parameters that were analyzed could account for these cognitive changes. The data demonstrate that learning and memory processes in the hippocampus of young tau-P301L mice are not impaired and actually improved in the absence of marked phosphorylation of human tau. We conclude that protein tau plays an important beneficial role in normal neuronal processes of hippocampal memory, and conversely, that not tau mutations per se, but the ensuing hyperphosphorylation must be critical for cognitive decline in tauopathies.
引用
收藏
页码:3514 / 3523
页数:10
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