Spontaneous circling behavior and dopamine neuron loss in a genetically hypothyroid mouse

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Abstract

The genetically hypothyroid mouse, Tshrhyt, has a single point mutation resulting in a defective thyroid-stimulating hormone receptor, and therefore a non-functional thyroid gland. This is an autosomal recessive disorder and affected mice have been reported to have a number of somatic and behavioral deficits. This study reports a pronounced, spontaneous, asymmetrical circling behavior in the Tshrhyt mouse. The spontaneous circling behavior appeared in about 25% of the homozygous animals, in both males and females. The circling usually appeared by postnatal day 35 and continued throughout the lifespan of the animal. The circling was in one direction only, either clockwise or counterclockwise, with the directional preference being almost absolute. A stereological analysis of tyrosine hydroxylase immunoreactive neurons in the substantia nigra and adjacent ventral tegmental area of circling homozygous mice, non-circling homozygous mice and heterozygous mice revealed that the circlers had significantly fewer (40% reduction) midbrain dopamine neurons than those animals that did not circle. There was not an association between the direction of the circling and an asymmetry in the number of dopamine neurons in the midbrains of these mice. There was no difference in the number of dopamine neurons in the midbrain of the homozygous non-circlers and the heterozygous mice. These studies indicate that about 25% of genetically hypothyroid mice demonstrated a spontaneous, perseverative, unilateral circling behavior that was associated with a significant reduction in the number of their midbrain dopamine neurons. Thus congenitally hypothyroid mice are at risk for a reduction in the number of nigral dopamine neurons and an associated repetitive movement disorder.

Original languageEnglish
Pages (from-to)891-898
Number of pages8
JournalNeuroscience
Volume105
Issue number4
DOIs
StatePublished - Aug 22 2001

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Dopaminergic Neurons
Mesencephalon
Substantia Nigra
Thyrotropin Receptors
Ventral Tegmental Area
Movement Disorders
Tyrosine 3-Monooxygenase
Risk Reduction Behavior
Point Mutation
Thyroid Gland
Neurons

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Spontaneous circling behavior and dopamine neuron loss in a genetically hypothyroid mouse. / Kincaid, Anthony.

In: Neuroscience, Vol. 105, No. 4, 22.08.2001, p. 891-898.

Research output: Contribution to journalArticle

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abstract = "The genetically hypothyroid mouse, Tshrhyt, has a single point mutation resulting in a defective thyroid-stimulating hormone receptor, and therefore a non-functional thyroid gland. This is an autosomal recessive disorder and affected mice have been reported to have a number of somatic and behavioral deficits. This study reports a pronounced, spontaneous, asymmetrical circling behavior in the Tshrhyt mouse. The spontaneous circling behavior appeared in about 25{\%} of the homozygous animals, in both males and females. The circling usually appeared by postnatal day 35 and continued throughout the lifespan of the animal. The circling was in one direction only, either clockwise or counterclockwise, with the directional preference being almost absolute. A stereological analysis of tyrosine hydroxylase immunoreactive neurons in the substantia nigra and adjacent ventral tegmental area of circling homozygous mice, non-circling homozygous mice and heterozygous mice revealed that the circlers had significantly fewer (40{\%} reduction) midbrain dopamine neurons than those animals that did not circle. There was not an association between the direction of the circling and an asymmetry in the number of dopamine neurons in the midbrains of these mice. There was no difference in the number of dopamine neurons in the midbrain of the homozygous non-circlers and the heterozygous mice. These studies indicate that about 25{\%} of genetically hypothyroid mice demonstrated a spontaneous, perseverative, unilateral circling behavior that was associated with a significant reduction in the number of their midbrain dopamine neurons. Thus congenitally hypothyroid mice are at risk for a reduction in the number of nigral dopamine neurons and an associated repetitive movement disorder.",
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