Effects of hypothyroidism induced by perinatal exposure to PTU on rat behavior and synaptic gene expression

Kobayashi, Kumiko; Tsuji, Ryozo; Yoshioka, Takafumi; Kushida, Masahiko; Yabushita, Setsuko; Sasaki, Masashi; Mino, Terumasa; Seki, Takaki

doi:10.1016/j.tox.2005.04.012

Cited by 46 publications

(23 citation statements)

References 53 publications

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“…Another possibility is that hypothyroidism affected the formation of auditory startle response neural circuits, which are composed of cochlear root neurons, neurons in the nucleus reticularis pontis caudalis, and spinal motoneurons (Lee, et al, 1996). Thyroid hormones regulate the expression of genes involved in axonal growth, myelination, and synaptic formation (Barradas, et al, 2000;Knipper et al, 1998;Kobayashi et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Irreversible damage to auditory system functions caused by perinatal hypothyroidism in rats

Wada

Yumoto

Iso

2013

Neurotoxicology and Teratology

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We examined the effect of perinatal hypothyroidism on auditory function in rats using a prepulse inhibition paradigm. Pregnant rats were treated with the antithyroid drug methimazole (1-methyl-2-mercaptoimidazole) from gestational day 15 to postnatal day 21 via drinking water at concentrations (w/v) of 0 (control), 0.002 (low dose), or 0.02% (high dose). Rats from methimazole-treated mothers were tested at ages 1, 6, and 12 months using techniques to examine prepulse inhibition and startle response. The startle stimulus consisted of 40 ms of white noise at 115 dB, whereas the prepulse, which preceded the startle stimulus by 30 ms, consisted of 20 ms of white noise at 75, 85, or 95 dB. When the prepulse intensity was 75 or 85 dB, the high-dose group showed decreased prepulse inhibition percentages compared with the control and low-dose groups. The reduced percentages of prepulse inhibition did not return to control levels over the 12-month study period. In contrast, no differences in prepulse inhibition were observed among the three dose groups when prepulse intensity was 95 dB. Moreover, the high-dose group displayed excessive reaction to auditory startle stimuli compared with the other groups. Reductions in plasma free thyroxine and body weight gain were observed in the high-dose group. We conclude that perinatal hypothyroidism results in irreversible damage to auditory function in rats.

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Section: Discussionmentioning

confidence: 99%

Irreversible damage to auditory system functions caused by perinatal hypothyroidism in rats

Wada

Yumoto

Iso

2013

Neurotoxicology and Teratology

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“…Perinatal administration of PTU from GD18 to PN21 has been also shown to alter the expression levels of genes implicated in axonal growth and learning such as GAP-43 in the cerebral cortex and the muscarinic acethylcholine receptor M1 in the hippocampus at PN22. Although the expression pattern of these genes returned to normal levels in 9-week-old rats, the impairment of E-maze learning, that is considered to involve hippocampal or cerebral cortical function, persisted at weaning and after maturation (Kobayashi et al 2005). Therefore, the alterations in the hippocampal formation that occur during developmental hypothyroidism are critical for the neurological and behavioral defects in the postnatal period.…”

Section: Models Of Maternal Hypothyroidism and Hypothyroxinemiamentioning

confidence: 99%

Thyroid hormones, learning and memory

Rivas

Naranjo

2007

Genes Brain and Behavior

106

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Thyroid hormones (THs), T3 and T4, have many physiological actions and are essential for normal behavioral, intellectual and neurological development. THs have a broad spectrum of effects on the developing brain and mediate important effects within the CNS throughout life. Insufficient maternal iodine intake during gestation and TH deficiency during human development are associated to pathological alterations such as cretinism and mental retardation. In adulthood, thyroid dysfunction is related to neurological and behavioral abnormalities, including memory impairment. Analysis of different experimental models suggests that most of the effects on cognition as a result of thyroid dysfunction rely on hippocampal modifications. Insufficiency of THs during development thus alters hippocampal synaptic function and impairs behavioral performance of hippocampaldependent learning and memory tasks that persist in euthyroid adult animals. In the present review, we summarize the current knowledge obtained by clinical observations and experimental models that shows the importance of THs in learning and mnemonic processes.

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“…In addition, neurogenesis and neuronal migration begin at about embryonic day12 and are complete at lactation in the rat [4]. Brains of pups develop rapidly during pregnancy and lactation, and most of the brain structures observed in adult rats are formed by the third postnatal week [33]. Therefore, protein levels of signaling molecules in the EC of pups were primarily examined on PN 21 and 28.…”

Section: Discussionmentioning

confidence: 99%

Developmental Iodine Deficiency and Hypothyroidism Reduce Phosphorylation of Calcium/Calmodulin-Dependent Kinase II in the Rat Entorhinal Cortex

Wang

Hou

Dong

et al. 2010

Biol Trace Elem Res

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Iodine is essential for the synthesis of triiodothyronine (T₃) and thyroxine (T₄). Iodine deficiency leads to inadequate thyroid hormone. Hypothyroidism induced by iodine deficiency during gestation and postnatal period leads to cognitive deficits in learning and memory. However, the mechanism underlying these deficits is unclear. Calcium-dependent calmodulin kinase II (CaMKII) known as a potential memory molecule regulates important neuronal functions including learning and memory. Recent studies have shown that hypothyroidism alters phosphorylation of CaMKII in hippocampus or even in sympathetic ganglia of rats. Though the entorhinal cortex (EC) is an important functional structure within the neuronal network responsible for learning and memory, little is known about the effect of hypothyroidism on phosphorylation of CaMKII in the EC. Here, we report that iodine deficiency and propylthiouracil treatment through gestation and lactation reduce phosphorylation of CaMKII in the EC of pups. The increase of calcineurin, as well as reduction of neurogranin and calmodulin, may account for the reduced phosphorylation of CaMKII induced by developmental iodine deficiency and hypothyroidism. These findings in the EC may contribute to understanding the mechanisms that underlie impairment of learning and memory induced by developmental iodine deficiency and hypothyroidism.

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Effects of hypothyroidism induced by perinatal exposure to PTU on rat behavior and synaptic gene expression

Cited by 46 publications

References 53 publications

Irreversible damage to auditory system functions caused by perinatal hypothyroidism in rats

Irreversible damage to auditory system functions caused by perinatal hypothyroidism in rats

Thyroid hormones, learning and memory

Developmental Iodine Deficiency and Hypothyroidism Reduce Phosphorylation of Calcium/Calmodulin-Dependent Kinase II in the Rat Entorhinal Cortex

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