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Global deprivation of brain-derived neurotrophic factor in the CNS reveals an area-specific requirement for dendritic growth

Rauskolb, S., Zagrebelsky, M., Dreznjak, A., Deogracias, R., Matsumoto, T., Wiese, S., Erne, B., Sendtner, M., Schaeren-Wiemers, N., Korte, M. and Barde, Yves-Alain 2010. Global deprivation of brain-derived neurotrophic factor in the CNS reveals an area-specific requirement for dendritic growth. Journal of Neuroscience 30 (5) , pp. 1739-1749. 10.1523/JNEUROSCI.5100-09.2010

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Abstract

Although brain-derived neurotrophic factor (BDNF) is linked with an increasing number of conditions causing brain dysfunction, its role in the postnatal CNS has remained difficult to assess. This is because the bdnf-null mutation causes the death of the animals before BDNF levels have reached adult levels. In addition, the anterograde axonal transport of BDNF complicates the interpretation of area-specific gene deletion. The present study describes the generation of a new conditional mouse mutant essentially lacking BDNF throughout the CNS. It shows that BDNF is not essential for prolonged postnatal survival, but that the behavior of such mutant animals is markedly altered. It also reveals that BDNF is not a major survival factor for most CNS neurons and for myelination of their axons. However, it is required for the postnatal growth of the striatum, and single-cell analyses revealed a marked decreased in dendritic complexity and spine density. In contrast, BDNF is dispensable for the growth of the hippocampus and only minimal changes were observed in the dendrites of CA1 pyramidal neurons in mutant animals. Spine density remained unchanged, whereas the proportion of the mushroom-type spine was moderately decreased. In line with these in vivo observations, we found that BDNF markedly promotes the growth of cultured striatal neurons and of their dendrites, but not of those of hippocampal neurons, suggesting that the differential responsiveness to BDNF is part of a neuron-intrinsic program.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH301 Biology
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.jneurosci.org/site/misc/ifa_policies.xhtml#copyright (accessed 27/02/2014).
Publisher: Society for Neuroscience
ISSN: 0270-6474
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 05:21
URI: http://orca.cf.ac.uk/id/eprint/51122

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