Thyrotoropin receptor knockout changes monoaminergic neuronal system and produces methylphenidate-sensitive emotional and cognitive dysfunction

Mouri, Akihiro; Hoshino, Yuta; Narusawa, Shiho; Ikegami, Keisuke; Mizoguchi, Hideaki; Murata, Yoshiharu; Yoshimura, Takashi; Nabeshima, Toshitaka

doi:10.1016/j.psyneuen.2014.05.021

Cited by 26 publications

(14 citation statements)

References 60 publications

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“…It is also probable that TSH would have a direct effect on brain function since TSH receptors are found on the surface of some brain cells as well as the thyroid gland (61). In the TSH receptor (TSHR) knockout mouse, TSH-TSHR dysregulation was associated with behaviors similar to those observed in ADHD (62). In humans, a future study using exogenous administration of recombinant human TSH (rhTSH) to elevate rhTSH levels in the euthyroid state would be an informative control condition for comparison with the hypothyroid status in thyroidectomy patients.…”

Section: Discussionmentioning

confidence: 99%

Diminished Quality of Life and Increased Brain Functional Connectivity in Patients with Hypothyroidism After Total Thyroidectomy

Shin

Choi

Kim

et al. 2016

Thyroid

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Section: Discussionmentioning

confidence: 99%

Diminished Quality of Life and Increased Brain Functional Connectivity in Patients with Hypothyroidism After Total Thyroidectomy

Shin

Choi

Kim

et al. 2016

Thyroid

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“…The novel objection test was performed on mice to test cognitive memory as described previously. 48 Briefly, in the training session, we placed two objects in a box (30 cm × 30 cm × 35 cm high). The objects were a white lamp and a square bottle, the shapes and colors being different but sizes being almost the same.…”

Section: Methodsmentioning

confidence: 99%

Periodontitis induced by bacterial infection exacerbates features of Alzheimer’s disease in transgenic mice

et al. 2017

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Periodontitis is a localized infectious disease caused by periodontopathic bacteria, such as Porphyromonas gingivalis. Recently, it has been suggested that bacterial infections may contribute to the onset and the progression of Alzheimer’s disease (AD). However, we do not have any evidence about a causative relationship between periodontitis and AD. In this study, we investigated by using a transgenic mouse model of AD whether periodontitis evoked by P. gingivalis modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice. Levels of Amiloid β (Aβ) deposition, Aβ40, and Aβ42 in both the hippocampus and cortex were higher in inoculated APP-Tg mice than in control APP-Tg mice. Furthermore, levels of IL-1β and TNF-α in the brain were higher in inoculated mice than in control mice. The levels of LPS were increased in the serum and brain of P. gingivalis-inoculated mice. P. gingivalis LPS-induced production of Aβ40 and Aβ42 in neural cell cultures and strongly enhanced TNF-α and IL-1β production in a culture of microglial cells primed with Aβ. Periodontitis evoked by P. gingivalis may exacerbate brain Aβ deposition, leading to enhanced cognitive impairments, by a mechanism that involves triggering brain inflammation.

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“…3 TSH receptors are seen in the amygdala, cingulate gyrus, frontal cortex, hippocampus, hypothalamus, and thalamus, 97 and their action is different from that of TRs. 98 Moreover, the production of antibodies in GD is not limited to TRAb. Autoantibodies against thyroglobulin, 99 TPO, 99 D2, 100 insulin-like growth factor 1 receptor, 101 angiotensin II receptor type 1, 102 and 1-adrenergic and M2 muscarinic receptors 103 104 have all been described as elevated in GD, some with proposed pathogenic effects.…”

Section: Thyroid Antibodies and The Brainmentioning

confidence: 99%

The Long-Term Outcome of Treatment for Graves' Hyperthyroidism

Sjölin

Holmberg

Törring

et al. 2019

Thyroid

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Graves' disease (GD) is an autoimmune condition with elevated thyroid hormone levels and symptoms suggesting an affected brain. These symptoms often resolve with treatment but, for some patients, GD results in a long period of reduced wellbeing. The overall aim of this thesis is to characterize the consequences of GD with a special focus on the brain. Three studies were conducted with data from questionnaires and clinical assessments of patients with GD in both the hyperthyroid and the euthyroid phase. Paper I was a longitudinal cohort study that assessed long-term treatment results 6 10 years after the onset of GD. Among 1186 included patients, the 774 who were initially treated with antithyroid drugs had a 40% chance of being euthyroid without thyroid medication at follow-up. One in four patients did not feel fully recovered. Paper II was a longitudinal case-control study designed to characterize affective and cognitive symptoms in 65 premenopausal women with newly diagnosed untreated GD. At onset of GD, the patients were significantly more affected with depression, anxiety, and mental fatigue compared to controls. At follow-up after 15 months, these symptoms remained in a significant proportion of patients. Patients with eye symptoms or a history of psychiatric conditions were more likely to be affected with brain-related symptoms. Paper III was a longitudinal case-control study of 65 premenopausal women with newly diagnosed untreated GD designed to investigate the effect of GD on hippocampal volumes. At onset of GD, hippocampus and amygdala volumes of the patients were smaller compared to controls. These brain structures became larger with treatment and, after 15 months, only the left amygdala remained smaller than in controls. At inclusion, there was an inverse correlation between thyroid-stimulating hormone receptor antibody (TRAb) and the volumes of both amygdalae and the right hippocampus. There were also inverse correlations between TRAb and free triiodothyronine recovery and the recovery of most of the four assessed brain volumes. GD is a condition where a minority of patients can hope for a long-lasting restored thyroid function. A large proportion of GD patients do not feel recovered after 8 years. Mental fatigue is an important concept for understanding the brain-derived symptoms in GD. In summary, the studies demonstrate that Graves' hyperthyroidism has unexpected long-term consequences for many patients, provide extensive new data on the serious and chronic nature of GD, and show for the first time that GD is accompanied by reversible brain changes.

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Thyrotoropin receptor knockout changes monoaminergic neuronal system and produces methylphenidate-sensitive emotional and cognitive dysfunction

Cited by 26 publications

References 60 publications

Diminished Quality of Life and Increased Brain Functional Connectivity in Patients with Hypothyroidism After Total Thyroidectomy

Diminished Quality of Life and Increased Brain Functional Connectivity in Patients with Hypothyroidism After Total Thyroidectomy

Periodontitis induced by bacterial infection exacerbates features of Alzheimer’s disease in transgenic mice

The Long-Term Outcome of Treatment for Graves' Hyperthyroidism

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