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 fT (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.

Contribution of Hypothyroidism to Cognitive Impairment and Hippocampal Synaptic Plasticity Regulation in an Animal Model of Depression

“…Basal excitatory transmission, measured as the input-output relationship, was significantly increased in both hippocampal regions in slices obtained from the Wistar rats treated with PTU. The same effect of hypothyroidism was also shown in young male Sprague Dawley rats [24], while in the present study in WKY rats, which were used as a model of depression, PTU had no effect on the magnitude of fEPSPs. The increase in amplitude associated with the deficit of thyroid hormones in Wistar rats may result from presynaptic changes-for example, increased release of glutamate or postsynaptic changes-in the density or reactivity of postsynaptic receptors.…”

Presymptomatic Treatment With Andrographolide Improves Brain Metabolic Markers and Cognitive Behavior in a Model of Early-Onset Alzheimer’s Disease

“…This test was performed as previously described, and the conditions of the pool were the same as those of a Morris Water Maze (Chen et al, 2000; Salazar et al, 2017). Each animal was trained to one pseudorandom location of the platform per day for 5 days, with a new platform location each day.…”

Wnt‐induced activation of glucose metabolism mediates the in vivo neuroprotective roles of Wnt signaling in Alzheimer disease

“…This test was performed as previously described (Chen et al 2000;Salazar et al 2017), and the pool conditions of the pool were the same as those of a Morris Water Maze (Cisternas et al 2015). Each animal was trained for one pseudo-random location of the platform per day, for 5 days, with a new platform location each day.…”