title: Lateral habenula as a link between thyroid and serotoninergic system modiates depressive symptoms in hypothyroidism rats.
abstract: Depression-like behavior is observed in both rats and people with hypothyroidism, which suggests that altered thyroid hormone levels are closely associated with mental illness. Furthermore, decreased serotonin (5-hydroxytryptamine, 5-HT) levels are found in some brain regions of hypothyroid rats with depression-like behavior. However, the mechanism underlying the effects of hypothyroidism on the central serotonin system is unclear. The lateral habenula (LHb) is related to both the serotonin and thyroid systems and also plays an important role in the pathogenesis of depression. Our study aimed to disclose the role of the LHb in the onset of depression-like behavior in thyroidectomy (TD) rats. Forced swimming (FST) and open-field tests (OFT) were performed to measure behavioral changes in TD rats. The expression of β calmodulin-dependent protein kinase type II (β CaMKII) in the LHb, cytochrome C oxidase (COX) activity in the LHb and dorsal raphe nucleus (DRN), and 5-HT levels in the DRN were assayed. We found that TD rats exhibited depression-like behavior in the FST and OFT. Compared with the sham group, neural activity and the expression of β CaMKII in TD rats were higher in the LHb, and neural activity and 5-HT levels were lower in the DRN. Depressive behavior and decreased 5-HT levels in the DRN in TD rats were reversed by LHb lesioning. Our study indicates that depression-like behavior in TD rats can be attributed to decreased 5-HT levels in the DRN resulting from inhibition by an overactive LHb. The LHb mediates the effect of the thyroid system on 5-HT function in the DRN.
authors.affiliation: Department of Physiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, PR China; Department of Thyroid Surgery, Neuroscience Research Center, First Hospital of Jilin University, Changchun 130021, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, PR China.
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Feng
authors.affiliation: Department of Thyroid Surgery, Neuroscience Research Center, First Hospital of Jilin University, Changchun 130021, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Thyroid Surgery, Neuroscience Research Center, First Hospital of Jilin University, Changchun 130021, PR China.
authors.forename: Xiao Feng
authors.initials: XF
authors.lastname: Liu
authors.affiliation: Department of Physiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, PR China.
authors.forename: Ji Cheng
authors.initials: JC
authors.lastname: Li
authors.affiliation: Department of Physiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, PR China; Department of Thyroid Surgery, Neuroscience Research Center, First Hospital of Jilin University, Changchun 130021, PR China. Electronic address: zhua@jlu.edu.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000818:Animals; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003863:Depression / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D019262:Habenula / Q000293:injuries / Q000378:metabolism*; D007037:Hypothyroidism / Q000097:blood / Q000150:complications*; D009434:Neural Pathways / Q000503:physiopathology; D011903:Raphe Nuclei / Q000293:injuries / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013550:Swimming / Q000523:psychology; D013965:Thyroidectomy / Q000009:adverse effects; D013972:Thyrotropin / Q000097:blood
chemical_list: D012701:Serotonin; D013972:Thyrotropin; D003576:Electron Transport Complex IV; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; C517702:Camkk2 protein, rat
keywords: Depression-like behavior; Dorsal raphe nucleus; Forced swimming test; Hypothyroidism; Lateral habenula; Serotonin