Essential role of tau phosphorylation in adult hippocampal neurogenesis

Hong, Xiaoping; Peng, Caixia; Wei, Wei; Tian, Qing; Liu, Yinghua; Yao, Xiu-Qing; Zhang, Yao; Cao, Fuliang; Wang, Qun; Wang, Jian‐Zhi

doi:10.1002/hipo.20712

Cited by 78 publications

(62 citation statements)

References 48 publications

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“…One of the tau isoforms, Tau-3R, is expressed by adult newborn neurons (Fuster-Matanzo et al, 2012). Interestingly, phosphorylated tau + cells are co-expressed with two markers of newborn neurons, DCX and NeuroD, in both a temporal and spatial fashion (Fuster-Matanzo et al, 2009;Hong et al, 2010). It is thus possible that more may be learned about the alterations in neurogenesis in AD by using tau-based mouse models over amyloid-based models given the need for tau expression under normal physiological conditions.…”

Section: Alterations In Hippocampal Neurogenesis In Ad Mouse Modelsmentioning

confidence: 99%

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Ryan

Kelly

2016

Ageing Research Reviews

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a b s t r a c tIt is now well established, at least in animal models, that exercise elicits potent pro-cognitive and proneurogenic effects. Alzheimer's disease (AD) is one of the leading causes of dementia and represents one of the greatest burdens on healthcare systems worldwide, with no effective treatment for the disease to date. Exercise presents a promising non-pharmacological option to potentially delay the onset of or slow down the progression of AD. Exercise interventions in mouse models of AD have been explored and have been found to reduce amyloid pathology and improve cognitive function. More recent studies have expanded the research question by investigating potential pro-neurogenic and anti-inflammatory effects of exercise. In this review we summarise studies that have examined exercise-mediated effects on AD pathology, cognitive function, hippocampal neurogenesis and neuroinflammation in transgenic mouse models of AD. Furthermore, we attempt to identify the optimum exercise conditions required to elicit the greatest benefits, taking into account age and pathology of the model, as well as type and duration of exercise.© 2016 Elsevier B.V. All rights reserved. Please cite this article in press as: Ryan, S.M., Kelly, Á.M., Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer's disease. Ageing Res. Rev. (2016), http://dx

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Section: Alterations In Hippocampal Neurogenesis In Ad Mouse Modelsmentioning

confidence: 99%

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Ryan

Kelly

2016

Ageing Research Reviews

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“…However, the relationship between neurogenesis and phosphorylated tau protein received little attention. Our recent studies have shown that tau phosphorylation by GSK-3 can stimulate adult hippocampal neurogenesis [15]. In addition, another laboratory has also reported increased neurogenesis during tau hyperphosphorylation in THY-Tau22 mice [16].…”

Section: Introductionmentioning

confidence: 95%

“…Inhibition of GSK-3b was associated with a reduction in axon growth and a dramatic increase in growth cone size [29]. Recently we have demonstrated that activated GSK-3b can stimulate hippocampal neurogenesis in adult rat brain [15], but we still know little about the influence of GSK-3b on the SVZ neurogenesis.…”

Section: Introductionmentioning

confidence: 99%

Relationship of Adult Neurogenesis with Tau Phosphorylation and GSK-3β Activity in Subventricular Zone

et al. 2010

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Altered neurogenesis has been reported in Alzheimer disease (AD), the most common neurodegenerative disorder characterized with hyperphosphorylated tau and accumulation of β-amyloid (Aβ). Recent studies suggest that tau phosphorylation is essential for hippocampal neurogenesis, however, it is not known whether tau phosphorylation also play a role in neurogenesis of subventricular zone (SVZ), another main progenitor niche in the brain. Here, we examined the expression of phosphorylated tau (p-tau) in SVZ and analyzed the role of p-tau in adult SVZ neurogenesis. We found that the expression of p-tau increased during postnatal development and remains at a high level until adulthood, and the p-tau was colocalized with some SVZ neural precursors. However, up-regulating glycogen synthase kinase-3 (GSK-3), a crucial tau kinase, had no effect on SVZ neurogenesis in adult rat brain. The SVZ neurogenesis was also unaffected in tau knockout and human tau transgenic mice. These results suggest that tau phosphorylation and GSK-3 activation may not be essential for adult SVZ neurogenesis.

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“…Less studied, however, are the direct effects on adult hippocampal neurogenesis of proteins that, as tau, regulate the morphogenesis and functional integration of new neurons (Bullmann et al, 2007;Fuster-Matanzo et al, 2012;Hong et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory

Pristerà

Saraulli

Farioli-Vecchioli

et al. 2013

Neurobiology of Aging

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. a b s t r a c tDifferent pathological tau species are involved in memory loss in Alzheimer's disease, the most common cause of dementia among older people. However, little is known about how tau pathology directly affects adult hippocampal neurogenesis, a unique form of structural plasticity implicated in hippocampusdependent spatial learning and mood-related behavior. To this aim, we generated a transgenic mouse model conditionally expressing a pathological tau fragment (26e230 aa of the longest human tau isoform, or N-tau) in nestin-positive stem/progenitor cells. We found that N-tau reduced the proliferation of progenitor cells in the adult dentate gyrus, reduced cell survival and increased cell death by a caspase3eindependent mechanism, and recruited microglia. Although the number of terminally differentiated neurons was reduced, these showed an increased dendritic arborization and spine density. This resulted in an increase of anxiety-related behavior and an impairment of episodic-like memory, whereas less complex forms of spatial learning remained unaltered. Understanding how pathological tau species directly affect neurogenesis is important for developing potential therapeutic strategies to direct neurogenic instructive cues for hippocampal function repair.

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Essential role of tau phosphorylation in adult hippocampal neurogenesis

Cited by 78 publications

References 48 publications

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Relationship of Adult Neurogenesis with Tau Phosphorylation and GSK-3β Activity in Subventricular Zone

Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory

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