The Role of Thioredoxin Reductases in Brain Development

• DOI: 10.1371/journal.pone.0001813
• Publication Date: 2008-03-18T19:14:36Z
• Authors: Jonna Soerensen; Cemile Jakupoglu; Heike Beck; Heidi Förster; Jörg Schmidt; Wolfgang Schmahl; Ulrich Schweizer; Marcus Conrad; Markus Brielmeier
• Keywords: Mice, Knockout; 0301 basic medicine; 0303 health sciences; Movement Disorders; Thioredoxin-Disulfide Reductase; Science; Q; R; Brain; 610; Growth; Mice; 03 medical and health sciences; Medicine; Animals; Research Article; Cell Proliferation

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 thioredoxin reductases in brain using mice nervous (NS)-specific deletion cytosolic (Txnrd1) and mitochondrial (Txnrd2) reductase. While NS-specific Txnrd2 null develop normally, lacking Txnrd1 NS were significantly smaller displayed ataxia tremor. A striking patterned cerebellar hypoplasia was observed. Proliferation external granular layer (EGL) strongly reduced fissure formation laminar organisation cortex impaired rostral portion cerebellum. Purkinje cells ectopically located their dendrites stunted. Bergmann glial network disorganized showed a pronounced reduction fiber strength. Cerebellar did not result from increased apoptosis, but decreased proliferation granule cell precursors within EGL. Of note, neuron-specific inactivation hypoplasia, suggesting vital role for glia or neuronal precursor cells.