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Published on: November 20, 2015
Induction of hypothyroidism during early postnatal stages triggers a decrease in cognitive performance by decreasing
Paulina Salazar1, Pedro Cisternas2, Juan Francisco Codocedo1
1Centro de Envejecimiento y Regeneración (CARE UC), Departamento de Biología Celular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Insights
Early-life hypothyroidism in rats impairs learning and memory by affecting hippocampal plasticity and function. This study highlights the critical role of thyroid hormones in early brain development and cognitive performance.
Area of Science:
- Neuroscience
- Endocrinology
- Developmental Biology
Background:
- Thyroid hormones are crucial for brain development and function.
- Hypothyroidism, particularly in early life, can have lasting impacts on cognitive abilities.
- The specific effects of early-onset hypothyroidism on hippocampal function remain incompletely understood.
Purpose of the Study:
- To investigate the impact of early postnatal hypothyroidism on cognitive functions, focusing on the hippocampus.
- To assess learning and memory deficits in a rat model of early-onset hypothyroidism.
- To explore the underlying mechanisms, including hippocampal plasticity, glucose metabolism, and oxidative stress.
Main Methods:
- Hypothyroidism was induced in young rats using 6-propyl-2-thiouracil (PTU) from postnatal day 21 for 4 weeks.
- Cognitive performance was evaluated using the Morris Water Maze test.
- Hippocampal plasticity (LTP/LTD), glucose utilization, oxidative stress markers, and MAP2 expression were assessed.
Main Results:
- PTU-induced hypothyroidism significantly impaired learning and memory in rats.
- Cognitive deficits correlated with reduced hippocampal plasticity (LTP/LTD).
- Hypothyroidism led to decreased hippocampal glucose utilization, increased oxidative stress, and reduced MAP2 levels.
Conclusions:
- Early-onset hypothyroidism in rats causes significant cognitive impairment.
- These impairments are associated with altered hippocampal plasticity, reduced glucose metabolism, and increased oxidative stress.
- The findings underscore the critical role of thyroid hormones in early brain development and hippocampal function.
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.
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