The role of thioredoxin reductases in brain development.
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vor 16 Jahren
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.
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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