Hypothyroidism modulates activity, expression and cellular localization of nNOS during rat brain postnatal development

ELGUERO ME, KERSTING S, ALIPPE Y, FINOCCHIETTO PV, PERALTA JG, PODEROSO JJ, CARRERAS MC

Sao Pedro

Congreso; VII Meeting of the SFRBM South American Group. I Sao Paulo Advanced School on Redox Processes in Biomedicine.; 2011

SFRBM South American Group

Nitric oxide (NO) is a physiological mediator in the central nervous system. Previously, we demonstrated that neuronal nitric oxide synthase (nNOS) is translocated into mitochondria in late stages of fetal development and during the first postnatal days, regulating synaptogenesis and synaptic remodeling. The increase in mitochondrial NO and reactive oxygen species yield causes cell arrest after proliferation. Thyroid hormone deficiency 2-3 weeks after birth causes neurological abnormalities, such as a reduction in synaptogenesis and myelination as well as delayed cell differentiation and migration. Likewise, perinatal and early postnatal stages involve maximal sensitivity period to thyroid hormone in rat brain. To address the changes produced by hypothyroidism in nNOS and its mitochondrial translocation through brain development, pregnant rats were divided in two groups, control (C) and hypothyroid (H, methimazole 0.02% wt/vol, was given to the pregnant rats in drinking water from gestational day 9); pups were analyzed at 5, 15 and 30 postnatal days (P5-P15-P30). The body weight of C was clearly higher than of H: 12.8±0.5 vs 9.6±0.1 respectively at P5, and 146.3±10 vs 61.2±3 at P30. nNOS expression in mitochondrial and cytosolic brain fractions evaluated by WB demonstrated nNOS increase in H cytosol from P5 to P30 respect to C (1.5 fold p