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Thyroid hormone regulates the expression of SNAP-25 during rat brain development

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Abstract

Thyroid hormones are major regulators of postnatal brain development. Thyroid hormones act through nuclear receptors to modulate the expression of specific genes in the brain. We have used microarray analysis to identify novel responsive genes in 14-day-old hypothyroid rat brains, and discovered that synaptosomal-associated protein of 25 kDa (SNAP-25) was one of the thyroid hormone-responsive genes. SNAP-25 is a presynaptic plasma membrane protein and an integral component of the vesicle docking and fusion machinery mediating secretion of neurotransmitters and is required for neuritic outgrowth and synaptogenesis. Using microarray analysis we have shown that SNAP-25 was down-regulated in the hypothyroid rat brain compared with the age-matched controls. Real-time RT-PCR and western blotting analysis confirmed that SNAP-25 mRNA and protein levels decreased significantly in the developing hypothyroid rat brain. Our data suggest that in the developing rat brain, SNAP-25 expression is regulated by thyroid hormone, and thyroid hormone deficiency can cause decreased expression of SNAP-25 and this may on some level account for the impaired brain development seen in hypothyroidism.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

GABA:

γ-Aminobutyric acid

NCAM:

Neural cell adhesion molecule

NGF:

Nerve growth factor

Pcp-2:

Purkinje cell protein-2

PCR:

Polymerase chain reaction

PTU:

Propylthiouracil

SNAP-25:

Synaptosomal-associated protein of 25 kDa

SNARE:

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor

T3 :

Triiodothyronine

T4 :

Thyroxine

TR:

thyroid Hormone receptor

VAMP:

Vesicle-associated membrane protein

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Acknowledgments

This study was supported by a grant from the National Natural Science Foundation of China (30200127 and 30470819). We gratefully acknowledge Katie Robertson for helpful assistance and critical review of the manuscript.

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Authors and Affiliations

  1. Department of Endocrinology, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, P.R. China

    Hong-Mei Zhang & Qing Su

  2. Shanghai Institute of Endocrinology and Metabolism, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, P.R. China

    Min Luo

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  1. Hong-Mei Zhang
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Correspondence to Qing Su.

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Zhang, HM., Su, Q. & Luo, M. Thyroid hormone regulates the expression of SNAP-25 during rat brain development. Mol Cell Biochem 307, 169–175 (2008). https://doi.org/10.1007/s11010-007-9596-1

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