RRC ID 181
著者 Oh-Nishi A, Saji M, Furudate SI, Suzuki N.
タイトル Dopamine D(2)-like receptor function is converted from excitatory to inhibitory by thyroxine in the developmental hippocampus.
ジャーナル J Neuroendocrinol
Abstract The mechanism by which a lack of thyroid hormone in the early development of the brain causes permanent mental retardation in cretins is currently unknown. On the other hand, an abnormality in dopamine-related brain function is believed to underlie some forms of mental illness. In this study, we demonstrate that although the activation of a dopaminergic D(2)-like receptor inhibited glutamatergic transmission in the hippocampal slices of normal adult rats, indicating the inhibitory action of the D(2)-like receptor on glutamatergic transmission, it markedly enhanced glutamatergic transmission both in a mutant hypothyroid rat with a missense mutation in thyroglobulin and in hypothyroid rats treated with methylmercaptoimidazole (MMI), indicating the excitatory action of the D(2)-like receptor on glutamatergic transmission. Paired pulse facilitation of field excitatory postsynaptic potentials was reduced by the activation of the D(2)-like receptors from MMI-induced hypothyroid rats, suggesting a presynaptic locus of the excitatory action of the D(2)-like receptors. In normal rats, the excitatory D(2)-like dopamine receptors were observed in the developing stages and were completely replaced by normal inhibitory responses up to adulthood. Furthermore, the continuous supplement of thyroxine from birth exerted a normalising effect on the abnormal excitatory property of D(2)-like dopamine receptors in the hippocampal slices of MMI-treated hypothyroid rats. From these results, it is suggested that thyroxine may play a crucial role in reversing the excitatory property of D(2)-like dopaminergic receptors in the immature brain to an inhibitory one in the mature brain. Moreover, we suggest that the abnormal excitatory property of D(2)-like dopaminergic receptors may develop in response to a lack of thyroxine and may contribute to some central nervous system deficits, including cognitive dysfunctions accompanied by hypothyroidism.
巻・号 17(12)
ページ 836-45
公開日 2005-12-1
DOI 10.1111/j.1365-2826.2005.01381.x
PII JNE1381
PMID 16280031
MeSH Animals Congenital Hypothyroidism / drug therapy Congenital Hypothyroidism / physiopathology* Dopamine Agonists / pharmacology Excitatory Postsynaptic Potentials / drug effects Excitatory Postsynaptic Potentials / physiology Hippocampus / drug effects Hippocampus / growth & development* Hippocampus / physiology* Male Mutation, Missense Neural Inhibition / physiology* Organ Culture Techniques Quinpirole / pharmacology Rats Rats, Mutant Strains Rats, Wistar Receptors, Dopamine D1 / physiology Receptors, Dopamine D2 / physiology* Thyroglobulin / genetics Thyroxine / pharmacology Thyroxine / physiology*
IF 2.886
引用数 14
WOS 分野 ENDOCRINOLOGY & METABOLISM NEUROSCIENCES
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