Profile for Amyloid-β and Tau Expression in Primary Cortical Cultures from 3xTg-AD Mice

Vale, Carmen; Albrecht, Eva; Rubiolo, Juan A.; Vieytes, Mercedes R.; LaFerla, Frank M.; Botana, Luís M.

doi:10.1007/s10571-009-9482-3

Cited by 39 publications

(47 citation statements)

References 29 publications

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“…At seven days in vitro the AD cellular model shows increased expression of the principal neuropathological hallmarks of the disease, consisting on a marked increase in the levels of intracellular Aβ and phosphorylated tau isoforms [14]. All experiments and toxin-treatments were performed simultaneously in 3xTg-AD cultures and control NonTg neurons.…”

Section: Resultsmentioning

confidence: 99%

“…Primary cortical neurons were obtained from embryonic day 15-17 NonTg and homozygous 3xTg-AD mice as previously described [14]. Briefly, cerebral cortex were removed and dissociated by mild trypsinization, followed by mechanical titration in a DNAse solution (0.005% w/v) containing a soybean trypsin inhibitor (0.05% w/v) at 37ºC.…”

Section: Primary Cortical Neuronsmentioning

confidence: 99%

“…Samples of cell lysates with 20 µg of total protein were resolved in gel loading buffer (50 mM TrisHCl, 100 mM dithiothreitol, 2% SDS, 20% glycerol, 0.05% bromophenol blue, pH 6.8) by SDS-PAGE and transferred onto PVDF membranes (Millipore). The Snap i.d protein detection system was used for blocking and antibody incubation as previously described [14]. The primary antibodies were applied at the concentrations shown in Table 1.…”

Section: Western Blottingmentioning

confidence: 99%

“…In order to do this, primary cortical neurons derived from the 3xTg-AD mice, which present a temporal profile of amyloid-beta and tau overexpression [14], were used and the long-term effect of the toxin on receptor expression and Aβ and tau pathologies was evaluated in this cellular model. Moreover, so far no reports on the effect of long term exposure to gymnodimine have been released.…”

Section: Introductionmentioning

confidence: 99%

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The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an <i>in Vitro</i> Model of Alzheimer Disease

Albrecht¹,

Vale²,

Vieytes³

et al. 2011

Cell Physiol Biochem

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Gymnodimine (GYM) is a marine phycotoxin with a macrocyclic imine structure, isolated from extracts of the dinoflagellate Karenia selliformis known to act as a cholinergic antagonist with subtype selectivity. However, no data on the chronic effects of this compound has been reported so far. In this work, we evaluated the effect of long term exposure of cortical neurons to gymnodimine in the progress of Alzheimer disease (AD) pathology in vitro. Treatment of cortical neurons with 50 nM gymnodimine decreased the intracellular amyloid beta (Aβ) accumulation and the levels of the hyperphosphorylated isoforms of tau protein recognized by AT8 and AT100 antibodies. These results are suggested to be mediated by the increase in the inactive isoform of the glycogen synthase kinase-3 (phospho GSK-3 Ser9), the decrease in the levels of the active isoform of the ERK1/2 kinase and the increase in acetylcholine (Ach) synthesis elicited by long term exposure of cortical neurons to the toxin. Moreover, gymnodimine decreased glutamate-induced neurotoxicity in vitro. Altogether these results indicate that the marine phycotoxin gymnodimine may constitute a valuable tool for the development of drugs to treat neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Primary Cortical Neuronsmentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an <i>in Vitro</i> Model of Alzheimer Disease

Albrecht¹,

Vale²,

Vieytes³

et al. 2011

Cell Physiol Biochem

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“…Clearly, a better understanding of how dysregulation of neuronal Ca(2+) handling contributes to neurodegeneration and neuroprotection in AD is needed as Ca(2+) signalling modulators are targets of great interest as potential AD therapeutics [26]. It is also showed that Amyloid-beta and Tau Expression relate to calcium (Ca (2+» [27].…”

Section: Discussionsmentioning

confidence: 99%

Learning the local molecular pattern of Alzheimer's disease by non-negative matrix factorization

Kong

Mou

et al. 2010

The 2010 International Conference on Green Circuits and Systems

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Gene microarray technology is an effective tool to monitor simultaneous activity of multiple cellular pathways from thousands of genes in a single chip. Many clustering methods have been developed to identify groups of genes or experimental conditions that exhibit similar expression patterns from gene expression data, such as hierarchical clustering, k-means, and self-organizing maps (SOM). The limitations of these clustering algorithms are: they group genes (or conditions) based on global similarities in their expression profiles and only assign each gene to a single cluster. In this work we present a biclustering method nonnegtive matrix factorization (NMF) to avoid the above drawbacks and discover the local molecular pattern from gene expression datasets of Alzheimer's disease (AD). NMF can be applied to reduce the dimensionality of the data and describe the data as a positive linear combination of a reduced number of factors. By applying a sparseness enforcement variable into classical NMF, the more local structures with meaningful biological information inherent in the data are captured by clustering genes and samples simultaneously, and the classification of samples is well improved. The analysis and discussion of the identified local structures demonstrated that they related many pathways which play a prominent role in AD and the activation patterns to AD phenotypes.

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SIRT1 Overexpression in Mouse Hippocampus Induces Cognitive Enhancement Through Proteostatic and Neurotrophic Mechanisms

Corpas

Revilla

Ursulet³

et al. 2016

Mol Neurobiol

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SIRT1 induces cell survival and has shown neuroprotection against amyloid and tau pathologies in Alzheimer's disease (AD). However, protective effects against memory loss or the enhancement of cognitive functions have not yet been proven. We aimed to investigate the benefits induced by SIRT1 overexpression in the hippocampus of the AD mouse model 3xTg-AD and in control non-transgenic mice. A lentiviral vector encoding mouse SIRT1 or GFP, selectively transducing neurons, was injected into the dorsal CA1 hippocampal area of 4-month-old mice. Six-month overexpression of SIRT1 fully preserved learning and memory in 10-month-old 3xTg-AD mice. Remarkably, SIRT1 also induced cognitive enhancement in healthy non-transgenic mice. Neuron cultures of 3xTg-AD mice, which show traits of AD-like pathology, and neuron cultures from non-transgenic mice were also transduced with lentiviral vectors to analyze beneficial SIRT1 mechanisms. We uncovered novel pathways of SIRT1 neuroprotection through enhancement of cell proteostatic mechanisms and activation of neurotrophic factors not previously reported such as GDNF, present in both AD-like and healthy neurons. Therefore, SIRT1 may increase neuron function and resilience against AD.

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Profile for Amyloid-β and Tau Expression in Primary Cortical Cultures from 3xTg-AD Mice

Cited by 39 publications

References 29 publications

The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an <i>in Vitro</i> Model of Alzheimer Disease

The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an <i>in Vitro</i> Model of Alzheimer Disease

Learning the local molecular pattern of Alzheimer's disease by non-negative matrix factorization

SIRT1 Overexpression in Mouse Hippocampus Induces Cognitive Enhancement Through Proteostatic and Neurotrophic Mechanisms

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