Neurogenesis and cell cycle‐reactivated neuronal death during pathogenic tau aggregation
Open Access
- 3 January 2008
- journal article
- Published by Wiley in Genes, Brain and Behavior
- Vol. 7 (s1), 92-100
- https://doi.org/10.1111/j.1601-183x.2007.00377.x
Abstract
The aim of the present study was to investigate the relation between neurogenesis, cell cycle reactivation and neuronal death during tau pathology in a novel tau transgenic mouse line THY-Tau22 with two frontotemporal dementia with parkinsonism linked to chromosome-17 mutations in a human tau isoform. This mouse displays all Alzheimer disease features of neurodegeneration and a broad timely resolution of tau pathology with hyperphosphorylation of tau at younger age (up to 6 months) and abnormal tau phosphorylation and tau aggregation in aged mice (by 10 months). Here, we present a follow-up of cell cycle markers with aging in control and transgenic mice from different ages. We show that there is an increased neurogenesis during tau hyperphosphorylation and cell cycle events during abnormal tau phosphorylation and tau aggregation preceding neuronal death and neurodegeneration. However, besides phosphorylation, other mechanisms including tau mutations and changes in tau expression and/or splicing may be also involved in these mechanisms of cell cycle reactivation. Altogether, these data suggest that cell cycle events in THY-Tau22 are resulting from neurogenesis in young animals and cell death in older ones. It suggests that neuronal cell death in such models is much more complex than believed.Keywords
This publication has 75 references indexed in Scilit:
- Immunohistological markers for staging neurogenesis in adult hippocampusCell and tissue research, 2007
- Regulation of phosphorylation of tau by cyclin‐dependent kinase 5 and glycogen synthase kinase‐3 at substrate levelFEBS Letters, 2006
- Alzheimer's Disease-Like Tau Neuropathology Leads to Memory Deficits and Loss of Functional Synapses in a Novel Mutated Tau Transgenic Mouse without Any Motor DeficitsThe American Journal of Pathology, 2006
- Cell-Cycle Markers in a Transgenic Mouse Model of Human Tauopathy: Increased Levels of Cyclin-Dependent Kinase Inhibitors p21Cip1 and p27Kip1The American Journal of Pathology, 2006
- Age-Dependent Neurofibrillary Tangle Formation, Neuron Loss, and Memory Impairment in a Mouse Model of Human Tauopathy (P301L)Journal of Neuroscience, 2005
- Tau Suppression in a Neurodegenerative Mouse Model Improves Memory FunctionScience, 2005
- Mitotic-like Tau Phosphorylation by p25-Cdk5 Kinase ComplexPublished by Elsevier BV ,2003
- Tau is a candidate gene for chromosome 17 frontotemporal dementiaAnnals of Neurology, 1998
- Neuropathological stageing of Alzheimer-related changesActa Neuropathologica, 1991
- Universal control mechanism regulating onset of M-phaseNature, 1990