Yuji Gamo

I.c.v. administration of orexin-A induces an antidepressive-like effect through hippocampal cell proliferation.

A decrease in orexin-A (OX-A) levels has been reported to be associated with depression. It is also well known that stress and depression can disrupt neurogenesis in the dentate gyrus of the hippocampus; however, it is unclear how OX-A is involved in depression and/or neurogenesis. In the present study, we investigated the effect of i.c.v. administration of OX-A on the forced swimming test (FST), an accepted behavioral screen of antidepressant-like activity, and on the cell proliferation with bromodeoxyuridine (BrdU) in the dentate gyrus at 4 days after i.c.v. administration of OX-A. OX-A administration (140 pmol/mouse) led to a significant reduction in animal immobility in the FST, without affecting spontaneous locomotor activities or serum corticosterone levels. In addition, the number of BrdU-positive cells in the dentate gyrus was significantly increased in OX-A-treated mice in vivo; however, OX-A did not affect the percentage of doublecortin-positive cells in the dentate gyrus. The proliferation of neural progenitor cells derived from rat fetal brain was not affected by OX-A treatment in vitro, and the orexin receptor 1 (OXR1) protein was not expressed in these cells. Treatment with the OXR1 antagonist SB-334867 (30 mg/kg, i.p.) blocked both the OX-A-induced decrease in the immobility of FST and increase in BrdU-positive. Moreover, the OX-A-induced increase in neuropeptide Y (NPY)-positive cells in the hilus of the dentate gyrus was blocked by SB-334867. These results suggest that OX-A induces an antidepressive-like effect, at least in part, via the enhancement of cell proliferation in the dentate gyrus. These effects of OX-A also may be partly relevant to the regulation of the NPY system in the hilus of the dentate gyrus.

Discrepancy Between Clinical Course and Drug-Induced Lymphocyte Stimulation Tests in a Case of Saireito-Induced Liver Injury Accompanied by Sjögren Syndrome

BACKGROUND Saireito consists of components of shosaikoto and goreisan. There are several reports of liver injury caused by shosaikoto and saireito, whereas cases caused by goreisan are rarely seen. PATIENT A 70-year-old woman suffered from sicca of the eyes and oral cavity that arose in 2003. In June 2004, we diagnosed her as having Sjögren syndrome on the basis of Schirmers test, salivary scintigraphy, presence of anti-SS-A/Ro antibody, and subjective symptoms. Although a muscarinic agonist was commenced, her sicca symptoms did not improve. INTERVENTIONS In February 2008, 7.5 g/day of shosaikoto extract granules (for ethical use, Tsumura & Co., Tokyo, Japan) was introduced. Her symptoms and laboratory data did not change. The next month, the treatment was replaced by 9.0 g/day of saireito extract granules (for ethical use, Tsumura & Co., Tokyo, Japan). RESULTS After 10 weeks, elevation of liver enzymes was observed. On suspicion of drug-induced liver injury (DILI), saireito was withdrawn, and the patients liver enzymes returned to normal the next month. Drug-induced lymphocyte stimulation tests (DLSTs) for saireito, shosaikoto, and goreisan were all positive. CONCLUSIONS The clinical course suggested allergy to the goreisan component of saireito. It is important to be aware of the limitation of DLST as a diagnostic tool for DILI, especially for herbal medicines.