title: The bidirectional effects of hypothyroidism and hyperthyroidism on anxiety- and depression-like behaviors in rats.
abstract: Thyroid hormone disorders have long been linked to depression, but the causal relationship between them remains controversial. To address this question, we established rat models of hypothyroidism using (131)iodine ((131)I) and hyperthyroidism using levothyroxine (LT4). Serum free thyroxine (FT4) and triiodothyronine (FT3) significantly decreased in the hypothyroid of rats with single injections of (131)I (5mCi/kg). These rats exhibited decreased depression-like behaviors in forced swimming test and sucrose preference tests, as well as decreased anxiety-like behaviors in an elevated plus maze. Diminished levels of brain serotonin (5-HT) and increased levels of hippocampal brain-derived neurotrophic factor (BDNF) were found in the hypothyroid rats compared to the control saline-vehicle administered rats. LT4 treatment reversed the decrease in thyroid hormones and depression-like behaviors. In contrast, hyperthyroidism induced by weekly injections of LT4 (15μg/kg) caused a greater than 10-fold increase in serum FT4 and FT3 levels. The hyperthyroid rats exhibited higher anxiety- and depression-like behaviors, higher brain 5-HT level, and lower hippocampal BDNF levels than the controls. Treatment with the antidepressant imipramine (15mg/kg) diminished serum FT4 levels as well as anxiety- and depression-like behaviors in the hyperthyroid rats but led to a further increase in brain 5-HT levels, compared with the controls or the hypothyroid rats. Together, our results suggest that hypothyroidism and hyperthyroidism have bidirectional effects on anxiety- and depression-like behaviors in rats, possibly by modulating hippocampal BDNF levels.
authors.affiliation: School of Life Sciences, Yunnan University, Kunming 650091, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China; Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Dafu
authors.initials: D
authors.lastname: Yu
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, 230026, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, Yunnan University, Kunming 650091, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China; Physiological Department, Kunming Medical University, Kunming 650500, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Tianchao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Lv
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China.
authors.forename: Qixin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China.
authors.forename: Yuexiong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Xuexian
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: He
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in Southwest China, and Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in Southwest China, and Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201, China.
authors.forename: Jijun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Kunhua
authors.initials: K
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Yunnan University, Kunming 650091, China; School of Life Sciences, University of Science and Technology of China, Hefei, 230026, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China. Electronic address: lxu@vip.163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China. Electronic address: talktomaomao@163.com.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Mao
mesh_terms: D000818:Animals; D001007:Anxiety / Q000097:blood / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003863:Depression / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism; D006980:Hyperthyroidism / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D007037:Hypothyroidism / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D013963:Thyroid Hormones; D012701:Serotonin
keywords: Anxiety; Brain-derived neurotrophic factor; Depression; Hyperthyroidism; Hypothyroidism