title: Yokukansan promotes hippocampal neurogenesis associated with the suppression of activated microglia in Gunn rat.
abstract: BACKGROUND
  The pathophysiology of schizophrenia (SCZ) remains unclear, and its treatment is far from ideal. We have previously reported that yokukansan (YKS), which is a traditional Japanese medicine, is effective as an adjunctive therapy for SCZ. However, the mechanisms underlying the action of YKS have not yet been completely elucidated. A recent meta-analysis study has shown that adjuvant anti-inflammatory drugs are effective for SCZ treatment, and it has been proposed that some of the cognitive deficits associated with inflammation may in part be related to inflammation-induced reductions in adult hippocampal neurogenesis. Although certain ingredients of YKS have potent anti-inflammatory activity, no study has determined if YKS has anti-inflammatory properties.
  
  
  METHODS
  Using the Gunn rat, which has been reported as a possible animal model of SCZ, we investigated whether YKS affects cognitive dysfunction in an object-location test and the suppression of microglial activation and neurogenesis in the hippocampus.
  
  
  RESULTS
  We found that YKS ameliorated spatial working memory in the Gunn rats. Furthermore, YKS inhibited microglial activation and promoted neurogenesis in the hippocampal dentate gyrus of these rats. These results suggest that the ameliorative effects of YKS on cognitive deficits may be mediated in part by the suppression of the inflammatory activation of microglia.
  
  
  CONCLUSIONS
  These findings shed light on the possible mechanism underlying the efficacy of YKS in treating SCZ.
authors.forename: Motohide
authors.initials: M
authors.lastname: Furuya
authors.affiliation: Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan. miyanyan@med.shimane-u.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyaoka
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tsumori
authors.forename: Kristian
authors.initials: K
authors.lastname: Liaury
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Hashioka
authors.forename: Rei
authors.initials: R
authors.lastname: Wake
authors.forename: Keiko
authors.initials: K
authors.lastname: Tsuchie
authors.forename: Michiyo
authors.initials: M
authors.lastname: Fukushima
authors.forename: Satoko
authors.initials: S
authors.lastname: Ezoe
authors.forename: Jun
authors.initials: J
authors.lastname: Horiguchi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000187:drug effects*; D018613:Microscopy, Confocal; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D011911:Rats, Gunn; D017208:Rats, Wistar; D012559:Schizophrenia / Q000503:physiopathology*
chemical_list: D004365:Drugs, Chinese Herbal; C524644:Yi-Gan San