title: The role of thioredoxin reductases in brain development.
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.
authors: Department of Comparative Medicine, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg, Germany.
authors: Jonna
authors: J
authors: Soerensen
authors: Cemile
authors: C
authors: Jakupoglu
authors: Heike
authors: H
authors: Beck
authors: Heidi
authors: H
authors: Förster
authors: Jörg
authors: J
authors: Schmidt
authors: Wolfgang
authors: W
authors: Schmahl
authors: Ulrich
authors: U
authors: Schweizer
authors: Marcus
authors: M
authors: Conrad
authors: Markus
authors: M
authors: Brielmeier
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D049109:Cell Proliferation; D006128:Growth; D051379:Mice; D018345:Mice, Knockout; D009069:Movement Disorders / Q000201:enzymology / Q000235:genetics; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*
chemical_list: D013880:Thioredoxin-Disulfide Reductase