The role of thioredoxin reductases in brain development

Jonna Soerensen, Cemile Jakupoglu, Heike Beck, Heidi Förster, Jörg Schmidt, Wolfgang Schmahl, Ulrich Schweizer, Marcus Conrad, Markus Brielmeier

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere1813
JournalPLoS ONE
Volume3
Issue number3
DOIs
StatePublished - 19 Mar 2008
Externally publishedYes

Fingerprint

Dive into the research topics of 'The role of thioredoxin reductases in brain development'. Together they form a unique fingerprint.

Cite this