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Neurotrophin‐4/5 Promotes Survival and Differentiation of Rat Striatal Neurons Developing in Culture

Neurotrophin‐4/5 Promotes Survival and Differentiation of Rat Striatal Neurons Developing in Culture Cultures of dissociated striatal neurons from fetal rats were prepared, and were grown in the presence of neurotrophin‐4/5 (NT‐4/5) as well as the other known neurotrophins, nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF) and neurotrophin‐3 (NT‐3). We found that acute administration of NT‐4/5 to 7‐day‐old cultures stimulates the hydrolysis of phosphatidylinositol, an event involved in neurotrophin signal transduction. Growth of striatal cultures in the presence of NT‐4/5 resulted in increased cell survival, as indicated by elevations in cell number, protein content, and a measure of mitochondrial enzyme activity (MTT assay). NT‐4/5 increased GABA uptake and staining intensity in these cultures, as indicated by GABA immunocytochemistry, indicating a trophic action on GABAergic neurons, the predominant neuron type in the striatum. To further identify responsive cell populations we analysed for calretinin, a calcium‐binding protein known to colocalize with GABA in a number of neuronal cells. In cultures prepared from rats of embryonic day 15, NT‐4/5 strongly increased the number of calretinin‐positive cells as well as calretinin levels, as determined by Western blot analysis. When the cultures were prepared from embryonic day 18 rats, NT‐4/5 very strongly increased the morphological differentiation of calretinin‐positive cells, whereas the increase in cell number was less prominent. All effects produced by NT‐4/5 were mimicked by BDNF with similar potency. NT‐3 was less effective than NT‐4/5 and BDNF, and its effects were limited to cultures prepared from embryonic day 15 rats, suggesting a role in the regulation of cell survival at early developmental stages. NGF did not affect any of the measured parameters. Our findings identify NT‐4/5 as potent neurotrophic factor for striatal neurons, able to promote their survival and differentiation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

Neurotrophin‐4/5 Promotes Survival and Differentiation of Rat Striatal Neurons Developing in Culture

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References (66)

Publisher
Wiley
Copyright
Copyright © 1994 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
DOI
10.1111/j.1460-9568.1994.tb00559.x
Publisher site
See Article on Publisher Site

Abstract

Cultures of dissociated striatal neurons from fetal rats were prepared, and were grown in the presence of neurotrophin‐4/5 (NT‐4/5) as well as the other known neurotrophins, nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF) and neurotrophin‐3 (NT‐3). We found that acute administration of NT‐4/5 to 7‐day‐old cultures stimulates the hydrolysis of phosphatidylinositol, an event involved in neurotrophin signal transduction. Growth of striatal cultures in the presence of NT‐4/5 resulted in increased cell survival, as indicated by elevations in cell number, protein content, and a measure of mitochondrial enzyme activity (MTT assay). NT‐4/5 increased GABA uptake and staining intensity in these cultures, as indicated by GABA immunocytochemistry, indicating a trophic action on GABAergic neurons, the predominant neuron type in the striatum. To further identify responsive cell populations we analysed for calretinin, a calcium‐binding protein known to colocalize with GABA in a number of neuronal cells. In cultures prepared from rats of embryonic day 15, NT‐4/5 strongly increased the number of calretinin‐positive cells as well as calretinin levels, as determined by Western blot analysis. When the cultures were prepared from embryonic day 18 rats, NT‐4/5 very strongly increased the morphological differentiation of calretinin‐positive cells, whereas the increase in cell number was less prominent. All effects produced by NT‐4/5 were mimicked by BDNF with similar potency. NT‐3 was less effective than NT‐4/5 and BDNF, and its effects were limited to cultures prepared from embryonic day 15 rats, suggesting a role in the regulation of cell survival at early developmental stages. NGF did not affect any of the measured parameters. Our findings identify NT‐4/5 as potent neurotrophic factor for striatal neurons, able to promote their survival and differentiation.

Journal

European Journal of Neuroscience – Wiley

Published: Nov 1, 1994

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