Prophylactic effects of sulforaphane on depression-like behavior and dendritic changes in mice after inflammation.
Inflammation plays a role in the pathophysiology of depression. Sulforaphane (SFN), an isothiocyanate compound derived from broccoli, is a potent activator of the NF-E2-related factor-2 (Nrf2), which plays a role in inflammation. In this study, we examined whether the prevention effects of SFN in lipopolysaccharide (LPS) induced depression-like behavior in mice. Pretreatment with SFN significantly blocked an increase in the serum tumor necrosis factor-α (TNF-α) level and an increase in microglial activation of brain regions after a single administration of LPS (0.5 mg/kg). Furthermore, SFN significantly potentiated increased serum levels of IL-10 after LPS administration. In the tail-suspension test and forced swimming test, SFN significantly attenuated an increase of the immobility time after LPS administration. In addition, SFN significantly recovered to control levels for LPS-induced alterations in the proteins such as brain-derived neurotrophic factor, postsynaptic density protein 95 and AMPA receptor 1 (GluA1) and dendritic spine density in the brain regions. Finally, dietary intake of 0.1% glucoraphanin (a glucosinolate precursor of SFN) food during the juvenile and adolescence could prevent the onset of LPS-induced depression-like behaviors and dendritic spine changes in the brain regions at adulthood. In conclusion, these findings suggest that dietary intake of SFN-rich broccoli sprout has prophylactic effects on inflammation-related depressive symptoms. Therefore, supplementation of SFN-rich broccoli sprout could be prophylactic vegetable to prevent or minimize the relapse by inflammation in the remission state of depressed patients.
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Ji-Chun
JC
Zhang
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Wei
W
Yao
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Chao
C
Dong
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Chun
C
Yang
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Qian
Q
Ren
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Min
M
Ma
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Mei
M
Han
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Jin
J
Wu
Innovation Division, KAGOME CO., LTD., Nasushiobara, Tochigi 329-2762, Japan.
Yusuke
Y
Ushida
Innovation Division, KAGOME CO., LTD., Nasushiobara, Tochigi 329-2762, Japan.
Hiroyuki
H
Suganuma
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan. Electronic address: hashimoto@faculty.chiba-u.jp.
Kenji
K
Hashimoto
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D001937:Brassica / Q000737:chemistry; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein / Q000235:genetics / Q000378:metabolism; D005961:Glucosinolates / Q000494:pharmacology; D007096:Imidoesters / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D016753:Interleukin-10 / Q000097:blood; D017879:Isothiocyanates / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010091:Oximes; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D013454:Sulfoxides; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; D005961:Glucosinolates; D007096:Imidoesters; D016753:Interleukin-10; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D010091:Oximes; D018091:Receptors, AMPA; D013454:Sulfoxides; D014409:Tumor Necrosis Factor-alpha; C501447:Dlg4 protein, mouse; C016766:sulforaphane; C119494:glucoraphanin
Brain-derived neurotrophic factor; Depression; Inflammation; Nrf2; Prevention; Sulforaphane; Synaptogenesis