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Soerensen, J. ; Jakupoglu, C. ; Beck, H.* ; Förster, H. ; Schmidt, J. ; Schmahl, W.* ; Schweizer, U.* ; Conrad, M. ; Brielmeier, M.

The role of thioredoxin reductases in brain development.

PLoS ONE 3:e1813 (2008)
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Open Access Gold
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The thioredoxin-dependent system is an essential regulator of cellular redox balance. Since oxidative stress has been linked with neurodegenerative disease, we studied the roles of thioredoxin reductases in brain using mice with nervous system (NS)-specific deletion of cytosolic (Txnrd1) and mitochondrial (Txnrd2) thioredoxin reductase. While NS-specific Txnrd2 null mice develop normally, mice lacking Txnrd1 in the NS were significantly smaller and displayed ataxia and tremor. A striking patterned cerebellar hypoplasia was observed. Proliferation of the external granular layer (EGL) was strongly reduced and fissure formation and laminar organisation of the cerebellar cortex was impaired in the rostral portion of the cerebellum. Purkinje cells were ectopically located and their dendrites stunted. The Bergmann glial network was disorganized and showed a pronounced reduction in fiber strength. Cerebellar hypoplasia did not result from increased apoptosis, but from decreased proliferation of granule cell precursors within the EGL. Of note, neuron-specific inactivation of Txnrd1 did not result in cerebellar hypoplasia, suggesting a vital role for Txnrd1 in Bergmann glia or neuronal precursor cells.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 3, Issue: 3, Pages: , Article Number: e1813 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Reviewing status Peer reviewed