title: Depression can be prevented by astaxanthin through inhibition of hippocampal inflammation in diabetic mice.
abstract: The critical factor considered in a depression induced by diabetes is the inflammation eliciting hippocampal, amygdala and thalamic neuronal injury. Therefore, inhibiting inflammatory reactions in the brain and reducing neuronal injury can alleviate depression in rodents suffering from diabetes mellitus. The oral administration of astaxanthin has been employed in emotional disorders and diabetic complications due to its anti-depressant, anti-inflammatory and anti-apoptotic functions. However, it has not been reported whether astaxanthin can improve diabetes-related depression-like behavior, and its potential mechanisms have not been elucidated. The objective of the present study is to elucidate the effect of astaxanthin on depression in diabetic mice and to understand the underlying molecular mechanisms. In this study, experimental diabetic mice were given a single intraperitoneal injection of streptozotocin (STZ, 150mg/kg, dissolved in citrate buffer) after fasting for 12h. The diabetic model was assessed 72h after STZ injection, and mice with a fasting blood glucose level more than or equal to 16.7mmol/L were used in this study, and oral astaxanthin (25mg/kg) was provided uninterrupted for ten weeks. Depression-like behavior was evaluated by the tail suspension test (TST) and forced swimming test (FST). The glial fibrillary acidic protein (GFAP) and cleaved caspase-3-positive cells were measured by immunohistochemistry, and the western blotting was used to test the protein levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and cyclooxygenase (COX-2). The results showed that astaxanthin had an anti-depressant effect on diabetic mice. Furthermore, we observed that astaxanthin significantly reduced the number of GFAP-positive cells in the hippocampus and hypothalamus, and also the expression of cleaved caspase-3 in the hippocampus, amygdala and hypothalamus was decreased as well. Moreover, astaxanthin could down-regulate the expression of IL-6, IL-1β and COX-2 in the hippocampus. These findings suggest that the mechanism of astaxanthin in preventing depression in diabetic mice involves the inhibition of inflammation/inflammation inhibition, thereby protecting neurons in hippocampus, amygdala and hypothalamus against hyperglycemic damage.
authors.affiliation: Laboratory of Morphology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Laboratory of Morphology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Laboratory of Morphology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Hu
authors.affiliation: Laboratory of Morphology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory of Morphology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China; Department of Pathogen Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Ren-Xian
authors.initials: RX
authors.lastname: Tang
authors.affiliation: Department of Pathogen Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China. Electronic address: zky02@163.com.
authors.forename: Kui-Yang
authors.initials: KY
authors.lastname: Zheng
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China; Department of Genetics, Research Center for Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China. Electronic address: biosongyuanjian@126.com.
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Song
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003863:Depression / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000523:psychology; D004353:Drug Evaluation, Preclinical; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007031:Hypothalamus / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D011897:Random Allocation; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D005904:Glial Fibrillary Acidic Protein; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D024341:Xanthophylls; C528900:glial fibrillary astrocytic protein, mouse; C577686:interleukin-6, mouse; C005948:astaxanthine; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Astaxanthin; Depression; Diabetes; Inflammation; Injury