Effects of chronic dysthyroidism on activity and exploration

Roca, Josefina Sala; Martí-Carbonell, Maria Assumpció; Garau, A; Darbra, Sònia; Balada, Ferran

doi:10.1016/s0031-9384(02)00815-6

Cited by 16 publications

(18 citation statements)

References 42 publications

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“…Rather, some of our results pointed to increased T 3 signaling resulting in enhanced pain perception (Edmondson et al, 1990;Bruno et al, 2005Bruno et al, , 2006. However, in contrast to hy- perthyroid rodents (Redei et al, 2001;Sala-Roca et al, 2002), there was no indication for hyperactivity in Mct8 Ϫ/y mice as shown by unaltered locomotion. We thus speculate that neurons in specific brain regions with direct access to the increased circulating T 3 levels may be exposed to enhanced T 3 signaling, if their T 3 uptake is independent of Mct8.…”

Section: Discussioncontrasting

confidence: 52%

Neuronal 3′,3,5-Triiodothyronine (T₃) Uptake and Behavioral Phenotype of Mice Deficient inMct8, the Neuronal T₃Transporter Mutated in Allan–Herndon–Dudley Syndrome

Wirth¹,

Roth²,

et al. 2009

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Thyroid hormone transport into cells requires plasma membrane transport proteins. Mutations in one of these, monocarboxylate transporter 8 (MCT8), have been identified as underlying cause for the Allan-Herndon-Dudley syndrome, an X-linked mental retardation in which the patients also present with abnormally high 3Ј,3,5-triiodothyronine (T 3 ) plasma levels. Mice deficient in Mct8 replicate the thyroid hormone abnormalities observed in the human condition. However, no neurological deficits have been described in mice lacking Mct8. Therefore, we subjected Mct8-deficient mice to a comprehensive immunohistochemical, neurological, and behavioral screen. Several behavioral abnormalities were found in the mutants. Interestingly, some of these behavioral changes are compatible with hypothyroidism, whereas others rather indicate hyperthyroidism. We thus hypothesized that neurons exclusively dependent on Mct8 are in a hypothyroid state, whereas neurons expressing other T 3 transporters become hyperthyroid, if they are exposed directly to the high plasma T 3 . The majority of T 3 uptake in primary cortical neurons is mediated by Mct8, but pharmacological inhibition suggested functional expression of additional T 3 transporter classes. mRNAs encoding six T 3 transporters, including L-type amino acid transporters (LATs), were coexpressed with Mct8 in isolated neurons. We then demonstrated Lat2 expression in cultured neurons and throughout murine brain development. In contrast, LAT2 is expressed in microglia in the developing human brain during gestation, but not in neurons. We suggest that lack of functional complementation by alternative thyroid hormone transporters in developing human neurons precipitates the devastating neurodevelopmental phenotype in MCT8-deficient patients, whereas Mct8-deficient mouse neurons are functionally complemented by other transporters, for possibly Lat2.

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Section: Discussioncontrasting

confidence: 52%

Neuronal 3′,3,5-Triiodothyronine (T₃) Uptake and Behavioral Phenotype of Mice Deficient inMct8, the Neuronal T₃Transporter Mutated in Allan–Herndon–Dudley Syndrome

Wirth¹,

Roth²,

et al. 2009

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“…In line with the data presented here, Overstreet et al (25) have shown increased locomotor activity in iodine-deficient congenitally hypothyroid rats. In contrast, other authors did not find any increase in motor activity (26). In the hyt/hyt mouse model of hypothyroidism, no changes in motor activity have been reported (49).…”

Section: Discussionmentioning

confidence: 81%

“…In experimental models, transient perinatal hypothyroidism (from the end of pregnancy to weaning) causes attention-deficit and hyperactive neurobiological symptoms in adult animals (21)(22)(23)(24). In congenital hypothyroidism (hypothyroidism induced in the perinatal life and maintained chronically), conflicting evidences regarding motor hyperactivity have been published (25,26). In the case of perinatal hyperthyroidism, both transient and chronic models have been associated with hyperactivity in the adult life (26,27).…”

mentioning

confidence: 99%

“…In congenital hypothyroidism (hypothyroidism induced in the perinatal life and maintained chronically), conflicting evidences regarding motor hyperactivity have been published (25,26). In the case of perinatal hyperthyroidism, both transient and chronic models have been associated with hyperactivity in the adult life (26,27). However, very little is known relative to the possible genes regulated by thyroid hormone, which could be implicated in the appearance of the hyperactive phenotype, although it has been suggested that alterations in the dopaminergic and noradrenergic systems can underlay the effects of thyroid hormone (25,28,29).…”

mentioning

confidence: 99%

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Implication of the Endocannabinoid System in the Locomotor Hyperactivity Associated with Congenital Hypothyroidism

et al. 2008

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Alterations in motor functions are well-characterized features observed in humans and experimental animals subjected to thyroid hormone dysfunctions during development. Here we show that congenitally hypothyroid rats display hyperactivity in the adult life. This phenotype was associated with a decreased content of cannabinoid receptor type 1 (CB(1)) mRNA in the striatum and a reduction in the number of binding sites in both striatum and projection areas. These findings suggest that hyperactivity may be the consequence of a thyroid hormone deficiency-induced removal of the endocannabinoid tone, normally acting as a brake for hyperactivity at the basal ganglia. In agreement with the decrease in CB(1) receptor gene expression, a lower cannabinoid response, measured by biochemical, genetic and behavioral parameters, was observed in the hypothyroid animals. Finally, both CB(1) receptor gene expression and the biochemical and behavioral dysfunctions found in the hypothyroid animals were improved after a thyroid hormone replacement treatment. Thus, the present study suggests that impairment in the endocannabinoid system can underlay the hyperactive phenotype associated with hypothyroidism.

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“…On the other hand, hypothyroidism did not affect activity, but did increase exploration. This increase in exploration was observed in activity independent behavioural parameters, such as head dipping and glancing (Sala-Roca et al, 2002).…”

Section: Wwwintechopencommentioning

confidence: 72%

Neurological Complications of Hypothyroidism

Türker¹,

Turker²,

Cengiz³

2012

Hypothyroidism - Influences and Treatments

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Effects of chronic dysthyroidism on activity and exploration

Cited by 16 publications

References 42 publications

Neuronal 3′,3,5-Triiodothyronine (T₃) Uptake and Behavioral Phenotype of Mice Deficient inMct8, the Neuronal T₃Transporter Mutated in Allan–Herndon–Dudley Syndrome

Neuronal 3′,3,5-Triiodothyronine (T₃) Uptake and Behavioral Phenotype of Mice Deficient inMct8, the Neuronal T₃Transporter Mutated in Allan–Herndon–Dudley Syndrome

Implication of the Endocannabinoid System in the Locomotor Hyperactivity Associated with Congenital Hypothyroidism

Neurological Complications of Hypothyroidism

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Effects of chronic dysthyroidism on activity and exploration

Cited by 16 publications

References 42 publications

Neuronal 3′,3,5-Triiodothyronine (T3) Uptake and Behavioral Phenotype of Mice Deficient inMct8, the Neuronal T3Transporter Mutated in Allan–Herndon–Dudley Syndrome

Neuronal 3′,3,5-Triiodothyronine (T3) Uptake and Behavioral Phenotype of Mice Deficient inMct8, the Neuronal T3Transporter Mutated in Allan–Herndon–Dudley Syndrome

Implication of the Endocannabinoid System in the Locomotor Hyperactivity Associated with Congenital Hypothyroidism

Neurological Complications of Hypothyroidism

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Resources

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Neuronal 3′,3,5-Triiodothyronine (T₃) Uptake and Behavioral Phenotype of Mice Deficient inMct8, the Neuronal T₃Transporter Mutated in Allan–Herndon–Dudley Syndrome

Neuronal 3′,3,5-Triiodothyronine (T₃) Uptake and Behavioral Phenotype of Mice Deficient inMct8, the Neuronal T₃Transporter Mutated in Allan–Herndon–Dudley Syndrome