Newsletter # 08
Cellular models
Progressive cell loss in neuronal populations is a pathological hallmark of neurodegenerative diseases (Jellinger and Stadelmann, 2001). Discovery of neurotrophin opened up a large and promising investigation field and they have been used for the treatment of several neurodegenerative diseases. The development of new compounds which can mimic neurotrophin effects and have drug-like propertises appears to be a promising strategy for the development of new therapeutics in neurodegenerative diseases. In addition to promoting neuronal survival, neurotrophins are also involved in neuronal differentiation and axonal outgrowth. Neuronal survival assay and neurite outgrowth assay are used in neurobiology to study the neurotophic effect of a new compound. Neurofit offers several models to test the neurotrophic potency of a compound on rat primary neuronal cultures.
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Compound testing :A primary culture of cortical neurons or spinal motor neurons are plated at low density in a defined medium. The compound is added and after 24h, 48h and/or 72h the number of surviving neurons is evaluated by an enzymatic assay measuring acid phosphatase activity, and the sprouting of neurons is evaluated by measuring the length of the principal neurite.
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Cortical neurons
24h after plating under control condition -
Spinal motor neurons
3 days after plating under control condition
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Dose-response curves from different neurotrophines on cortical neurons survival after 3 days of treatment. BDNF and bFGF are able to promote cortical neurons survival whereas GDNF and NGF are not
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BDNF (50 ng/ml) and PMA (10 nM), a PKC activator
increase the length of the major neurite on primary culture from cortical neurons -
BDNF at 50 ng/ml
increase the length of the major neurite on primary culture from spinal motor neurons
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