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

Rauskolb, Stefanie and Zagrebelsky, Marta and Dreznjak, Anita and Deogracias, Rubén and Matsumoto, Tomoya and Wiese, Stefan and Erne, Beat and Sendtner, Michael and Schaeren-Wiemers, Nicole and Korte, Martin 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.

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Official URL: http://edoc.unibas.ch/dok/A5259495

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Neurologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Neurologie
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Neurobiology (Schaeren-Wiemers)
05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Pharmacology/Neurobiology (Barde)
UniBasel Contributors:Barde, Yves-Alain and Schaeren-Wiemers, Nicole and Deogracias Pastor, Ruben
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Society for Neuroscience
ISSN:0270-6474
e-ISSN:1529-2401
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:27 Nov 2017 14:18
Deposited On:08 Jun 2012 06:51

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