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

Abstract

The role that thyroid hormone deficiency plays in depression and synaptic plasticity in adults has only begun to be elucidated. This paper analyzes the possible link between depression and hypothyroidism in cognitive function alterations, using Wistar–Kyoto (WKY—an animal model of depression) rats and control Wistar rats under standard and thyroid hormone deficiency conditions (propylthiouracil administration—PTU). A weakening of memory processes in the WKY rats is shown behaviorally, and in the reduction of long-term potentiation (LTP) in the dentate gyrus (DG) and CA1 hippocampal regions. PTU administration decreased LTP and increased basal excitatory transmission in the DG in Wistar rats. A decrease in short-term synaptic plasticity is shown by the paired-pulse ratio measurement, occurring during hypothyroidism in DG and CA1 in WKY rats. Differences between the strains may result from decreases in the p-CaMKII, p-AKT, and the level of acetylcholine, while in the case of the co-occurrence of depression and hypothyroidism, an increase in the p-ERK1-MAP seemed to be important. Obtained results show that thyroid hormones are less involved in the inhibition of glutamate release and/or excitability of the postsynaptic neurons in WKY rats, which may indicate a lower sensitivity of the hippocampus to the action of thyroid hormones in depression.

Changes in regulators of lipid metabolism in the brain: a study of animal models of depression and hypothyroidism

“…The models of depression and hypothyroidism used in this study were verified in our previous studies. In addition to the fact that the WKY rats are a well-described model of depression [22], in our research, conducted at the same time as the current study, we also confirmed the presence of pro-depressive behavior in the forced swim test, pro-anxiety behavior in the elevated plus-maze test and memory disturbances in the novel object recognition and novel object location test [14,31]. Moreover, in WKY rats, we also observed a reduction in long-term potentiation in the dentate gyrus and CA1 region of the hippocampus and in short-term synaptic plasticity in the CA1 region of the hippocampus in electrophysiological studies, which also indicates the presence of memory disturbances in WKY rats [14].…”

“…Samples were isolated and processed according to a protocol described previously [14]. In brief, brain structures such as the frontal cortex and hippocampus were homogenized in 2% SDS (BioShop, Burlington, ON, Canada) and prepared for the following analysis by mixing equal amounts of protein with loading buffer (Bio-Rad, CA, Hercules, CA, USA) before being boiled (5 min, 95 °C).…”

“…Adult-onset hypothyroidism also impairs the cholinergic system, presynaptic proteins involved in neurotransmitters' release, phosphatases activity, and adult hippocampal neurogenesis [12,13]. Our previous studies have shown, inter alia, that in the animal model of the coexistence of depression and hypothyroidism there is a stronger weakening of the mechanism of presynaptic neurotransmitter release than in models of depression or hypothyroidism alone [14].…”

Efeito da auriculoterapia chinesa sobre o humor de profissionais de saúde: estudo piloto

“…UFSM, Santa Maria, v11, e53: p. 1-21, 2021 consumo de álcool, exacerbando estados negativos, principalmente na ressaca, 27 em problemas de saúde como no hipotireoidismo e na depressão. 28 No entanto, tais variáveis não comprometeram o desfecho obtido neste estudo.…”

The Correlation Between Thyroid Function, Frontal Gray Matter, and Executive Function in Patients With Major Depressive Disorder

“…On the one hand, it is recognized that disturbance in thyroid homeostasis may manifest various psychiatric symptoms, including depression, anxiety, mood swings, and psychosis, probably due to thyroid hormone-mediated interference in metabolic processes and intracellular signaling pathways ( 11 ). For example, decreased T4 levels have been linked to reduced neuronal actin polymerization in cultured astrocytes.…”