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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Attention deficit/hyperactivity disorder (ADHD) has been reported in association with resistance to thyroid hormone, a disease caused by a mutation in the thyroid hormone receptor β (TRβ) gene. TRβ is a key protein mediating down-regulation of thyrotropin (TSH) expression by 3,3',5-tri-iodothyronine (T3), an active form of thyroid hormone. Dysregulation of TSH and its receptor (TSHR) is implicated in the pathophysiology of ADHD but the role of TSHR remains elusive. Here, we clarified a novel role for TSHR in emotional and cognitive functions related to monoaminergic nervous systems. TSHR knockout mice showed phenotypes of ADHD such as hyperactivity, impulsiveness, a decrease in sociality and increase in aggression, and an impairment of short-term memory and object recognition memory. Administration of methylphenidate (1, 5 and 10. mg/kg) reversed impulsiveness, aggression and object recognition memory impairment. In the knockout mice, monoaminergic changes including decrease in the ratio of 3-methoxy-4-hydroxyphenylglycol/noradrenaline and increase in the ratio of homovanillic acid/dopamine were observed in some brain regions, accompanied by increase in the expression of noradrenaline transporter in the frontal cortex. When TSH was completely suppressed by the supraphysiological administration of T3 to the adult mice, some behavioral and neurological changes in TSHR KO mice were also observed, suggesting that these changes were not due to developmental hypothyroidism induced by the inactivation of TSHR but to the loss of the TSH-TSHR pathway itself. Taken together, the present findings suggest a novel role for TSHR in behavioral and neurological phenotypes of ADHD.

Original languageEnglish
Pages (from-to)147-161
Number of pages15
JournalPsychoneuroendocrinology
Volume48
DOIs
Publication statusPublished - 01-01-2014
Externally publishedYes

Fingerprint

Thyrotropin Receptors
Methylphenidate
Attention Deficit Disorder with Hyperactivity
Thyroid Hormone Receptors
Aggression
Knockout Mice
Thyroid Hormone Resistance Syndrome
Norepinephrine Plasma Membrane Transport Proteins
Phenotype
Homovanillic Acid
Cognitive Dysfunction
Frontal Lobe
Thyrotropin
Hypothyroidism
Thyroid Hormones
Short-Term Memory
Cognition
Nervous System
Dopamine
Norepinephrine

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Mouri, Akihiro ; Hoshino, Yuta ; Narusawa, Shiho ; Ikegami, Keisuke ; Mizoguchi, Hiroyuki ; Murata, Yoshiharu ; Yoshimura, Takashi ; Nabeshima, Toshitaka. / Thyrotoropin receptor knockout changes monoaminergic neuronal system and produces methylphenidate-sensitive emotional and cognitive dysfunction. In: Psychoneuroendocrinology. 2014 ; Vol. 48. pp. 147-161.
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Thyrotoropin receptor knockout changes monoaminergic neuronal system and produces methylphenidate-sensitive emotional and cognitive dysfunction. / Mouri, Akihiro; Hoshino, Yuta; Narusawa, Shiho; Ikegami, Keisuke; Mizoguchi, Hiroyuki; Murata, Yoshiharu; Yoshimura, Takashi; Nabeshima, Toshitaka.

In: Psychoneuroendocrinology, Vol. 48, 01.01.2014, p. 147-161.

Research output: Contribution to journalArticle

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AU - Narusawa, Shiho

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