Changes in adult neurogenesis in neurodegenerative diseases: cause or consequence?

Thompson, Abigail; Boekhoorn, Karin; Dam, Andrew; Lucassen, Paul J.

doi:10.1111/j.1601-183x.2007.00379.x

Cited by 65 publications

(41 citation statements)

References 162 publications

(251 reference statements)

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“…However, it may also be attributed to a benefit of experiencing mild adversity during early development (Levine, 2000). Intriguingly, this behavioral resilience may be associated with neurogenesis in specific brain areas that have also been implicated in the efficacy of antidepressant treatment (Kozorovitskiy and Gould, 2004;Sahay and Hen, 2008;Thompson et al, 2008).…”

Section: Can Early Adversity Results In Resilience?mentioning

confidence: 96%

Non-Human Primates: Model Animals for Developmental Psychopathology

Nelson

Winslow

2008

Neuropsychopharmacol

100

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Non-human primates have been used to model psychiatric disease for several decades. The success of this paradigm has issued from comparable cognitive skills, brain morphology, and social complexity in adult monkeys and humans. Recently, interest in biological psychiatry has focused on similar brain, social, and emotional developmental processes in monkeys. In part, this is related to evidence that early postnatal experiences in human development may have profound implications for subsequent mental health. Non-human primate studies of postnatal phenomenon have generally fallen into three basic categories: experiential manipulation (largely manipulations of rearing), pharmacological manipulation (eg drug-induced psychosis), and anatomical localization (defined by strategic surgical damage). Although these efforts have been very informative each of them has certain limitations. In this review we highlight general findings from the non-human primate postnatal developmental literature and their implications for primate models in psychiatry. We argue that primates are uniquely capable of uncovering interactions between genes, environmental challenges, and development resulting in altered risk for psychopathology.

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Section: Can Early Adversity Results In Resilience?mentioning

confidence: 96%

Non-Human Primates: Model Animals for Developmental Psychopathology

Nelson

Winslow

2008

Neuropsychopharmacol

100

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“…Thus, we propose that, in MBNBs, hTau may sequester atypical PKC away from complexes requisite to maintain polarity and their selfrenewal, or it interferes directly with the process. Interestingly, recent reports suggest that excess Tau may differentially target neural stem cells in the dentate gyrus and the subventricular zone responsible for adult neurogenesis in the mouse and human patients (for review, see Thompson et al, 2008). Therefore, hTau toxicity on MBNBs may represent an analogous phenomenon in the fly but manifested in the embryo because of their unique developmental properties (Ito et al, 1997a).…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Tau on the Integrity and Function of Neurons Essential for Learning in Drosophila

Kosmidis¹,

Grammenoudi²,

Papanikolopoulou³

et al. 2010

J. Neurosci.

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Tauopathies are a heterogeneous group of neurodegenerative dementias involving perturbations in the levels, phosphorylation, or mutations of the microtubule-binding protein Tau. The heterogeneous pathology in humans and model organisms suggests differential susceptibility of neuronal types to wild-type (WT) and mutant Tau. WT and mutant human Tau-encoding transgenes expressed panneuronally in the Drosophila CNS yielded specific and differential toxicity in the embryonic neuroblasts that generate the mushroom body (MB) neurons, suggesting cell type-specific effects of Tau in the CNS. Frontotemporal dementia with parkinsonism-17-linked mutant isoforms were significantly less toxic in MB development. Tau hyperphosphorylation was essential for these MB aberrations, and we identified two novel putative phosphorylation sites, Ser 238 and Thr 245, on WT hTau essential for its toxic effects on MB integrity. Significantly, blocking putative Ser 238 and Thr 245 phosphorylation yielded animals with apparently structurally normal but profoundly dysfunctional MBs, because animals accumulating this mutant protein exhibited strongly impaired associative learning.Interestingly, the mutant protein was hyperphosphorylated at epitopes typically associated with toxicity and neurodegeneration, such as AT8, AT100, and the Par-1 targets Ser 262 and Ser 356 , suggesting that these sites in the context of adult intact MBs mediate dysfunction and occupation of these sites may precede the toxicity-associated Ser 238 and Thr 245 phosphorylation. The data support the notion that phosphorylation at particular sites rather than hyperphosphorylation per se mediates toxicity or dysfunction in a cell type-specific manner.

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“…However, Tau-dependent ablation of the MBs does not reflect a degenerative process because toxicity of the hyper-phosphorylated protein ostensibly blocked the MBNB to MB neuron transition in embryos, rather than induce loss of already extant ones. This type of toxicity may be akin to Tau-dependent loss of mammalian adult neural stem cells, a process that has been proposed to contribute to neuronal loss in tauopathies (reviewed in [78]). …”

Section: Wt Isoform Toxicity In the Cnsmentioning

confidence: 98%

The Power and Richness of Modelling Tauopathies in Drosophila

Papanikolopoulou

Skoulakis

2011

Mol Neurobiol

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Tauopathies are a group of neurodegenerative disorders characterised by altered levels of phosphorylation or mutations in the neuronal microtubule protein Tau. The heterogeneous pathology of tauopathies suggests differential susceptibility of different neuronal types to wild-type and mutant Tau. The genetic power and facility of the Drosophila model has been instrumental in exploring the molecular aetiologies of tauopathies, identifying additional proteins likely contributing to neuronal dysfunction and toxicity and novel Tau phosphorylations mediating them. Importantly, recent results indicate tissue- and temporal-specific effects on dysfunction and toxicity coupled with differential effects of distinct Tau isoforms within them. Therefore, they reveal an unexpected richness of the Drosophila model that, coupled with its molecular genetic power, will likely play a significant role in our understanding of multiple tauopathies potentially leading to their differential treatment.

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Changes in adult neurogenesis in neurodegenerative diseases: cause or consequence?

Cited by 65 publications

References 162 publications

Non-Human Primates: Model Animals for Developmental Psychopathology

Non-Human Primates: Model Animals for Developmental Psychopathology

Differential Effects of Tau on the Integrity and Function of Neurons Essential for Learning in Drosophila

The Power and Richness of Modelling Tauopathies in Drosophila

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