QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 29, 2006, 26(13):3514-3523; doi:10.1523/JNEUROSCI.5425-05.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Boekhoorn, K. Articles by Lucassen, P. J. Search for Related Content PubMed PubMed Citation Articles by Boekhoorn, K. Articles by Lucassen, P. J.

 Previous Article  |  Next Article 

Neurobiology of Disease
Improved Long-Term Potentiation and Memory in Young Tau-P301L Transgenic Mice before Onset of Hyperphosphorylation and Tauopathy

Karin Boekhoorn,¹ Dick Terwel,² Barbara Biemans,² Peter Borghgraef,² Olof Wiegert,¹ Ger J. A. Ramakers,³ Koos de Vos,³ Harm Krugers,¹ Takami Tomiyama,⁴ Hiroshi Mori,⁴ Marian Joels,¹ Fred van Leuven,² and Paul J. Lucassen¹

¹Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, 1098 SM Amsterdam, The Netherlands, ²Experimental Genetics Group, Department of Human Genetics, K. U. Leuven, B-3000 Leuven, Belgium, ³Netherlands Institute for Brain Research, 1105 A2 Amsterdam, The Netherlands, and ⁴Department of Neuroscience, Medical School, Abenoku, Osaka 545-8585, Japan

Correspondence should be addressed to Dr. Fred van Leuven, Department of Human Genetics, K. U. Leuven, Campus Gasthuisberg ON1-06.602 06, B-3000 Leuven, Belgium. Email: fredvl{at}med.kuleuven.be

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.

Key words: LTP; neurodegeneration; memory; dendate gyrus; neurogenesis; Golgi impregnation

---

Received Sept. 27, 2005; revised Feb. 10, 2006; accepted Feb. 13, 2006.

Correspondence should be addressed to Dr. Fred van Leuven, Department of Human Genetics, K. U. Leuven, Campus Gasthuisberg ON1-06.602 06, B-3000 Leuven, Belgium. Email: fredvl{at}med.kuleuven.be

This article has been cited by other articles:

				D. L. Champagne, R. C. Bagot, F. van Hasselt, G. Ramakers, M. J. Meaney, E. R. de Kloet, M. Joels, and H. Krugers Maternal Care and Hippocampal Plasticity: Evidence for Experience-Dependent Structural Plasticity, Altered Synaptic Functioning, and Differential Responsiveness to Glucocorticoids and Stress J. Neurosci., June 4, 2008; 28(23): 6037 - 6045. [Abstract] [Full Text] [PDF]

				D. Terwel, D. Muyllaert, I. Dewachter, P. Borghgraef, S. Croes, H. Devijver, and F. Van Leuven Amyloid Activates GSK-3{beta} to Aggravate Neuronal Tauopathy in Bigenic Mice Am. J. Pathol., March 1, 2008; 172(3): 786 - 798. [Abstract] [Full Text] [PDF]

				K. Sennvik, K. Boekhoorn, R. Lasrado, D. Terwel, S. Verhaeghe, H. Korr, C. Schmitz, T. Tomiyama, H. Mori, H. Krugers, et al. Tau-4R suppresses proliferation and promotes neuronal differentiation in the hippocampus of tau knockin/knockout mice FASEB J, July 1, 2007; 21(9): 2149 - 2161. [Abstract] [Full Text] [PDF]

				Z. Pu, H. J. Krugers, and M. Joels Corticosterone time-dependently modulates {beta}-adrenergic effects on long-term potentiation in the hippocampal dentate gyrus Learn. Mem., May 3, 2007; 14(5): 359 - 367. [Abstract] [Full Text] [PDF]

				T. Vandebroek, D. Terwel, T. Vanhelmont, M. Gysemans, C. Van Haesendonck, Y. Engelborghs, J. Winderickx, and F. Van Leuven Microtubule Binding and Clustering of Human Tau-4R and Tau-P301L Proteins Isolated from Yeast Deficient in Orthologues of Glycogen Synthase Kinase-3beta or cdk5 J. Biol. Chem., September 1, 2006; 281(35): 25388 - 25397. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help