title: Oral administration of inosine produces antidepressant-like effects in mice.
abstract: Inosine, a breakdown product of adenosine, has recently been shown to exert immunomodulatory and neuroprotective effects. We show here that the oral administration of inosine has antidepressant-like effects in two animal models. Inosine significantly enhanced neurite outgrowth and viability of primary cultured neocortical neurons, which was suppressed by adenosine A1 and A2A receptor agonists. Oral administration of inosine to mice transiently increased its concentration in the brain and enhanced neuronal proliferation in the dentate gyrus, accompanied by phosphorylation of mitogen-activated protein kinase and increase in transcript level of brain-derived neurotrophic factor. In stress models, oral inosine prevented an increase in immobility time in forced swim test after chronically unexpected stress and mitigated a reduction in sucrose preference after chronic social defeat stress. These results indicate that oral administration of inosine has the potential to prevent depressive disorder via adenosine receptors.
authors.affiliation: 1] Graduate School of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan [2] Department of Health and Sports Science, Nippon Medical School, Kawasaki, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Muto
authors.affiliation: 1] Department of Health and Sports Science, Nippon Medical School, Kawasaki, Japan [2] Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kawasaki, Japan.
authors.forename: Hosung
authors.initials: H
authors.lastname: Lee
authors.affiliation: 1] Department of Health and Sports Science, Nippon Medical School, Kawasaki, Japan [2] Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kawasaki, Japan.
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Lee
authors.affiliation: 1] Department of Health and Sports Science, Nippon Medical School, Kawasaki, Japan [2] Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kawasaki, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Uwaya
authors.affiliation: 1] Graduate School of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan [2] Department of Health and Sports Science, Nippon Medical School, Kawasaki, Japan.
authors.forename: Jonghyuk
authors.initials: J
authors.lastname: Park
authors.affiliation: 1] Department of Health and Sports Science, Nippon Medical School, Kawasaki, Japan [2] Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kawasaki, Japan [3] Kyoritsu Women's Junior College, Tokyo, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: 1] Department of Health and Sports Science, Nippon Medical School, Kawasaki, Japan [2] Department of Biochemistry and Cell Biology, Institute of Development and Aging Science, Graduate School of Medicine, Nippon Medical School, Kawasaki, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nagata
authors.affiliation: Graduate School of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohno
authors.affiliation: Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Ikuroh
authors.initials: I
authors.lastname: Ohsawa
authors.affiliation: Department of Health and Sports Science, Nippon Medical School, Kawasaki, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Mikami
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D003863:Depression / Q000503:physiopathology* / Q000517:prevention & control*; D007288:Inosine / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D018047:Receptors, Purinergic P1; D007288:Inosine