RT Journal Article T1 Nitric oxide synthase system in the brain development of neonatal hypothyroid rats A1 López Ramos, Juan Carlos A1 Martínez-Lara, Esther A1 Serrano, Julia A1 Fernández, Patricia A1 G. Parras, Gloria A1 Ruiz-Marcos, Antonio A1 Rodrigo, José K1 Hypothyroidism K1 Nitric oxide synthase K1 Nitrotyrosine K1 Brain development K1 Cerebral cortex K1 Rat AB Thyroid hormones play an important morphogenetic role during the fetal and neonatal periods and regulate numerous metabolic processes. In the central nervous system, they control myelination and overall brain development, regional gene expression, and regulation of oxygen consumption. Their deficiency in the fetal and neonatal periods causes severe mental retardation, due to lack of thyroid function, or to iodine deficiency. At the same time, nitric oxide is an atypical neurotransmitter that also has special relevance in neuronal developmentand plasticity and functions as a vasodilator, regulating cerebral blood flow. Although under physiological conditions it functions as a neuroprotector, in excess it can be neurotoxic. We have studied, by immunocytochemical and Western blot techniques, the evolution of the expression of neuronal and inducible isoforms of the enzyme nitric oxide synthase, and of nitrotyrosine as a marker of protein nitration produced by the presence of nitric oxide, during the early stages of postnatal brain development. We induced hypothyroidism by administering mercaptomethylimidazole to pregnant mothers, from the seventh day of gestation until the sacrifice of the offspring. The results show a delay in the evolution of the expression of the two isoforms of the enzyme nitric oxide synthase in hypothyroid animals, followed by an anomalous overexpression in later stages. Finally, the expression of nitrotyrosine follows an evolution that is synchronized with that shown by both isoenzymes in control and hypothyroid animals. PB Elsevier en nombre de IBRO YR 2024 FD 2024-10-24 LK https://hdl.handle.net/10433/22100 UL https://hdl.handle.net/10433/22100 LA en NO Neuroscience 565 (2025) 155–171 NO DGYCIT PM 98-0126-C02-01Comunidad de Madrid 08.5%0054%2000-1Caixa Foundation 99/077- 00Patronato para la Prevención y Atención a Personas con Minusvalías NO División de Neurociencias, Universidad Pablo de Olavide DS RIO RD May 22, 2026