title: Induction of hypothyroidism during early postnatal stages triggers a decrease in cognitive performance by decreasing hippocampal synaptic plasticity.
abstract: Thyroid hormones are vital in the control of multiple body functions, including the correct performance of the brain. Multiple diseases are associated with thyroid gland functioning, including hypothyroidism. To date, little is known regarding the effects of the establishment of this condition at a young age on brain function. Here, we evaluated the effect of hypothyroidism in an early postnatal stage in cognitive abilities with focus on the hippocampus. In our model, hypothyroidism was induced in young rats at 21days of age using 0.05% 6-propyl-2-thiouracil (PTU) for 4weeks reaching significantly lower levels of fT4(control: 1.337ng/dL±0.115, PTU: 0.050ng/dL±0.001). Following the induction of hypothyroidism, several cognitive tasks were assessed to investigate the effects of hypothyroidism on cognition performance. We determined that hypothyroidism triggers a significant dysfunction in learning and memory processes observed in the Morris Water Maze were the latency times were higher in PTU rats (controls: 37s; PTU: 57s). The cognitive impairment was correlated with a reduction in hippocampal plasticity with respect to both long-term potentiation (LTP) (control: 1.45, PTU: 1.00) and depression (LTD) (control: 0.71, PTU: 1.01). Furthermore, a decrease in the rate of glucose utilization (control: 223nmol∗mg of protein, PTU:148nmol∗mg of protein) was observed, along with an increase in oxidative stress and a decrease in MAP2 marker in the hippocampus. Our findings suggest that the induction of hypothyroidism in a young rat model alters numerous functions at the level of the hippocampus.
authors.affiliation: Centro de Envejecimiento y Regeneración (CARE UC), Departamento de Biología Celular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Paulina
authors.initials: P
authors.lastname: Salazar
authors.affiliation: Centro de Envejecimiento y Regeneración (CARE UC), Departamento de Biología Celular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; Universidad de Atacama, Facultad de Ciencias Naturales, Departamento de Química y Biología, Copayapu 485, Copiapó, Chile.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cisternas
authors.affiliation: Centro de Envejecimiento y Regeneración (CARE UC), Departamento de Biología Celular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Codocedo
authors.affiliation: Centro de Envejecimiento y Regeneración (CARE UC), Departamento de Biología Celular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile. Electronic address: ninestrosa@bio.puc.cl.
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects*; D011441:Propylthiouracil / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011441:Propylthiouracil; D005947:Glucose
keywords: Cognitive performance; Glucose metabolism; Hippocampus; Hypothyroidism