Fucoidan exerts antidepressant-like effects in mice via regulating the stability of surface AMPARs |
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Affiliation: | 1. Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China;2. Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, China;3. Department of Rehabilitation Medicine, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China;4. Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China;1. Department of Forensic Science, Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi 710061, PR China;2. Department of Anatomy & Neurobiology, University of California, Irvine, School of Medicine, Irvine, CA, USA;3. School of Forensic Medicine, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China;4. Department of Pharmacy Engineering, Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi 710061, PR China;1. Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India;2. Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India;3. Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam 781022, India;4. Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India;1. Food and Pharmacy College, Zhejiang Ocean University and Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, Zhejiang, Zhoushan 316022, China;2. Yanbian University School of Medicine, Jilin 133000, Yanji, China;1. Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China;2. Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China;3. Neurosurgery Department, Qilu Hospital, Shandong University, Wenhua Xi Road, Jinan, Shandong Province 250012, PR China;4. Department of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China |
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Abstract: | The inflammatory hypothesis is one of the most important mechanisms of depression. Fucoidan is a bioactive sulfated polysaccharide abundant in brown seaweeds with anti-inflammatory activity. However, the antidepressant effects of fucoidan on chronic stress-induced depressive-like behaviors have not been well elucidated. Here, we used two different depressive-like mouse models, lipopolysaccharide (LPS) and chronic restraint stress (CRS) models, to explore the detailed molecular mechanism underlying its antidepressant-like effects in C57BL/6J mice by combining multiple behavioral, molecular and immunofluorescence experiments. Adenovirus-mediated overexpression of caspase-1 and pharmacological inhibitors were also used to clarify the antidepressant mechanisms of fucoidan. We found that acute administration of fucoidan did not produce antidepressant effects in the tail suspension test (TST) and forced swim test (FST). Interestingly, chronic fucoidan administration not only dose-dependently reduced stress-induced depressive-like behaviors in the TST, FST, sucrose preference test (SPT), and novelty-suppressed feeding test (NSFT), but also alleviated the downregulation of brain-derived neurotrophic factor (BDNF)-dependent synaptic plasticity via inhibiting caspase-1-mediated inflammation in the hippocampus of mice. Moreover, fucoidan significantly ameliorated behavioral and synaptic plasticity abnormalities in the overexpression of caspase-1 in the hippocampus of mice. Furthermore, blocking BDNF abolished the antidepressant-like effects of fucoidan in mice. Therefore, our findings clearly indicate that fucoidan provides a potential supplementary noninvasive treatment for depression by inhibition of hippocampal inflammation. |
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Keywords: | Fucoidan Lipopolysaccharide Chronic restraint stress Caspase-1 BDNF AMPARs p.o." },{" #name" :" keyword" ," $" :{" id" :" kwrd0045" }," $$" :[{" #name" :" text" ," _" :" Per os i.p." },{" #name" :" keyword" ," $" :{" id" :" kwrd0055" }," $$" :[{" #name" :" text" ," _" :" Intraperitoneally TST" },{" #name" :" keyword" ," $" :{" id" :" kwrd0065" }," $$" :[{" #name" :" text" ," _" :" Tail suspension test FST" },{" #name" :" keyword" ," $" :{" id" :" kwrd0075" }," $$" :[{" #name" :" text" ," _" :" Forced swim test LPS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0085" }," $$" :[{" #name" :" text" ," _" :" Lipopolysaccharide CRS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0095" }," $$" :[{" #name" :" text" ," _" :" Chronic restraint stress SPT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0105" }," $$" :[{" #name" :" text" ," _" :" Sucrose preference test NSFT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0115" }," $$" :[{" #name" :" text" ," _" :" Novelty-suppressed feeding test mPFC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0125" }," $$" :[{" #name" :" text" ," _" :" Medial prefrontal cortex Hip" },{" #name" :" keyword" ," $" :{" id" :" kwrd0135" }," $$" :[{" #name" :" text" ," _" :" Hippocampus qRT-PCR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0145" }," $$" :[{" #name" :" text" ," _" :" Quantitative real-time PCR GAPDH" },{" #name" :" keyword" ," $" :{" id" :" kwrd0155" }," $$" :[{" #name" :" text" ," _" :" Glyceraldehyde-3-phosphate dehydrogenase Iba1" },{" #name" :" keyword" ," $" :{" id" :" kwrd0165" }," $$" :[{" #name" :" text" ," _" :" Ionized calcium binding adapter molecule 1 IL-1β" },{" #name" :" keyword" ," $" :{" id" :" kwrd0175" }," $$" :[{" #name" :" text" ," _" :" Interleukin-1beta IL-18" },{" #name" :" keyword" ," $" :{" id" :" kwrd0185" }," $$" :[{" #name" :" text" ," _" :" Interleukin-18 BDNF" },{" #name" :" keyword" ," $" :{" id" :" kwrd0195" }," $$" :[{" #name" :" text" ," _" :" Brain-derived neurotrophic factor CREB" },{" #name" :" keyword" ," $" :{" id" :" kwrd0205" }," $$" :[{" #name" :" text" ," _" :" cAMP response element binding protein AMPARs" },{" #name" :" keyword" ," $" :{" id" :" kwrd0215" }," $$" :[{" #name" :" text" ," _" :" α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors Bis(sulfosuccinimidyl)suberate AAV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0235" }," $$" :[{" #name" :" text" ," _" :" Adeno-associated virus GFP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0245" }," $$" :[{" #name" :" text" ," _" :" Green fluorescent protein CUS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0255" }," $$" :[{" #name" :" text" ," _" :" Chronic unpredictable stress NMDARs" },{" #name" :" keyword" ," $" :{" id" :" kwrd0265" }," $$" :[{" #name" :" text" ," $$" :[{" #name" :" italic" ," _" :" N" },{" #name" :" __text__" ," _" :" -methyl-" },{" #name" :" small-caps" ," _" :" d" },{" #name" :" __text__" ," _" :" -aspartate receptors |
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