Hypothyroidism in the developing rat brain is associated with marked oxidative stress and aberrant intraneuronal accumulation of neurofilaments

The effects of hypothyroidism on parameters of oxidative stress and on intr aneuronal distribution of neurofilaments have been investigated in the deve loping rat brain. Progressive hypothyroidism during the first 4 weeks of po stnatal development led to an increase in superoxide dismutase and catalase activity, decline in the level of glutathione and mitochondrial cytochrome c oxidase activity and increase in the level of (OH)-O-. radical along wit h enhanced protein carbonylation and lipid peroxidation. Immunocytochemical staining of cryostat sections of normal and hypothyroid cerebella from 25 day postnatal rats with anti neurofilament (NF) light chain (L) antibody sh owed aberrant accumulation of neurofilaments in the perikaryon of the hypot hyroid Purkinje neurons in contrast to relatively uniform distribution in t he controls. The morphological and biochemical alterations in the neurons o f the developing hypothyroid brain are comparable to those seen in several neurodegenerative diseases. (C) 2001 Elsevier Science Ireland Ltd and the J apan Neuroscience Society. All rights reserved.