Neural precursor-derived astrocytes of wobbler mice induce apoptotic death of motor neurons through reduced glutamate uptake

Diana, Valentina; Ottolina, Arianna; Botti, Francesca; Fumagalli, Elena; Calcagno, Eleonora; Paola, Massimiliano De; Cagnotto, Alfredo; Invernici, Gloria; Parati, Eugenio; Curti, Daniela; Mennini, Tiziana

doi:10.1016/j.expneurol.2010.06.008

Cited by 22 publications

(18 citation statements)

References 41 publications

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“…Since heterozygous mice do not show any phenotypic difference compared to homozygous healthy littermates, heterozygous founders were determined by genotyping [19].…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

et al. 2012

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Stem Cell (SC) therapy is one of the most promising approaches for the treatment of Amyotrophic Lateral Sclerosis (ALS). Here we employed Super Paramagnetic Iron Oxide nanoparticles (SPIOn) and Hoechst 33258 to track human Amniotic Fluid Cells (hAFCs) after transplantation in the lateral ventricles of wobbler (a murine model of ALS) and healthy mice. By in vitro, in vivo and ex vivo approaches we found that: 1) the main physical parameters of SPIOn were maintained over time; 2) hAFCs efficiently internalized SPIOn into the cytoplasm while Hoechst 33258 labeled nuclei; 3) SPIOn internalization did not alter survival, cell cycle, proliferation, metabolism and phenotype of hAFCs; 4) after transplantation hAFCs rapidly spread to the whole ventricular system, but did not migrate into the brain parenchyma; 5) hAFCs survived for a long time in the ventricles of both wobbler and healthy mice; 6) the transplantation of double-labeled hAFCs did not influence mice survival.

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“…Since heterozygous mice do not show any phenotypic difference compared to homozygous healthy littermates, heterozygous founders were determined by genotyping [19].…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

et al. 2012

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“…Glutamate levels in the brain of wobbler mice were found to be similar to levels in controls and even slightly downregulated in the spinal cord (Krieger et al 1991). On the other hand, neural precursor cell (NPC)-derived astrocytes were found to release excessive levels of glutamate into the medium in cell culture while at the same time having lower concentrations of intracellular glutamate (Diana et al 2010). Binding to the metabotropic glutamate receptor was found to be unaltered whereas the binding to NMDA receptors, Kainate-receptors and AMPA-receptors was increased in the wobbler cervical spinal cord (Tomiyama et al 1994).…”

Section: The Wobbler Phenotypementioning

confidence: 99%

“…In the cervical spinal cord from wobbler mice a reduced level of neuronal glutamate receptor EAAC1 has been shown, while the glial glutamate transporters GLT-1 and GLAST were shown in normal levels (Bigini et al 2001). In vivo, grafted astrocytes derived from NPCs showed reduced immunoreactivity for both GLT-1 and GLAST (Diana et al 2010). These astrocytes also displayed a reduced uptake of d -[2,3- 3 H]-aspartic acid most likely due to a lower number of glutamate receptors (Diana et al 2010).…”

Section: The Wobbler Phenotypementioning

confidence: 99%

The wobbler mouse, an ALS animal model

2013

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This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking similarities to ALS. The cellular effects of the wobbler mutation, cellular transport defects, neurofilament aggregation, neuronal hyperexcitability and neuroinflammation closely resemble human ALS. Now, 57 years after the first report on the wobbler mouse we summarize the progress made in understanding the disease mechanism and testing various therapeutic approaches and discuss the relevance of these advances for human ALS. The identification of the causative mutation linking the wobbler mutation to a vesicle transport factor and the research focussed on the cellular basis and the therapeutic treatment of the wobbler motor neuron degeneration has shed new light on the molecular pathology of the disease and might contribute to the understanding the complexity of ALS.

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“…In particular, it appears that TDP-43 plays a pivotal role in many forms of MND, and this protein, being implicated in some forms of dementia, exerts a contributory role in a wider number of neurodegenerative diseases 27. Moreover, a careful examination of the pathological SCs in these new animal models, as well as of the surrounding niche, could reveal abnormalities that may influence reparative mechanisms, as already suggested in tgSOD-1 NPs,28 wobbler mice,29 and in the bone marrow of sporadic ALS patients 30…”

Section: Stem Cells and New Pharmacotherapeutic Strategies: Approachimentioning

confidence: 84%

Amyotrophic lateral sclerosis: applications of stem cells – an update

Cova

Silani

2010

SCCAA

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Neurodegenerative diseases are a growing public health challenge, and amyotrophic lateral sclerosis (ALS) remains a fatal incurable disease. The advent of stem cell therapy has opened new horizons for both researchers and ALS patients, desperately looking for a treatment. ALS must be considered a systemic disease affecting many cell phenotypes besides motor neurons, even outside the central nervous system. Cell replacement therapy needs to address the specific neurobiological issues of ALS to safely and efficiently reach clinical settings. Moreover, the enormous potential of induced pluripotent cells directly derived from patients for modeling and understanding the pathological mechanisms, in correlation with the discoveries of new genes and animal models, provides new opportunities that need to be integrated with previously described transplantation strategies. Finally, a careful evaluation of preclinical data in conjunction with wary patient choice in clinical trials needs to be established in order to generate meaningful results.

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Neural precursor-derived astrocytes of wobbler mice induce apoptotic death of motor neurons through reduced glutamate uptake

Cited by 22 publications

References 41 publications

Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

The wobbler mouse, an ALS animal model

Amyotrophic lateral sclerosis: applications of stem cells – an update

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Neural precursor-derived astrocytes of wobbler mice induce apoptotic death of motor neurons through reduced glutamate uptake

Cited by 22 publications

References 41 publications

Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

The wobbler mouse, an ALS animal model

Amyotrophic lateral sclerosis: applications of stem cells &ndash; an update

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Amyotrophic lateral sclerosis: applications of stem cells – an update