INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Hypothyroidism modulates activity, expression and cellular localization of nNOS during rat brain postnatal development.
Autor/es:
ELGUERO ME, ALIPPE Y, FINOCCHIETTO PV, PODEROSO JJ, CARRERAS MC
Lugar:
San Carlos de Bariloche, Rio Negro
Reunión:
Congreso; Second South American Spring Symposium in Signal Transductionnand Molecular Medicine; 2012
Resumen:
Previously, we demonstrated neuronal nitric oxide synthase (nNOS) presents a mitochondrial localization regulated during fetal and postnatal brain development. In this manner NO levels could regulate proliferation, differentiation or cell death through mitochondrial oxidants balance. 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) receiving methimazole 0.02% wt/vol in drinking water from gestational day 9. Pups were analyzed at 5, 15 and 30 postnatal days (P5-P15-P30). nNOS expression and activity was evaluated in mitochondrial and cytosolic brain fractions. Both were significantly increased in mitochondrial fractions of hypothyroid P5-P15 respect to control rats, consecuent with a period in which strong mitochondrial NO regulation could be determinant. It correlates with synaptogenesis and synaptic remodeling in brain postnatal development. The body weight of H was clearly lower than C: 9.6±0.1 vs 12.8±0.5 respectively at P5, and 61.2±3 vs 146.3±10 at P30, and it was partially reverted by T3 XXX administration at maximal mitochondrial nNOS expression time (p10-P15). To address the effect of mitochondrial NO on redox balance, NO-dependent superoxide anion and H2O2 production was evaluated and showed an increase in P15 H (3.2 fold in H vs C),  as a result of respiratory chain inhibition. These changes were reverse by pumping infution of LNAME 30mg/Kg/day from postnatal day 10 to 15. Oxidants produced contributed to the complex I inactivation whose activity determined spectrophotometricaly was significantly inhibited in hypothyroidism at P5 and P15 stages, recovered from P15 up P30 by LNAME delivering as same way hormonal replacement with T3. We can conclude that inhibition of nNOS activity in this critical period rescued mitochondrial metabolism and cellular redox status as well as the systemic regulation with effects similar to the action of thyroid hormone