title: Establishment of an intermittent cold stress model using Tupaia belangeri and evaluation of compound C737 targeting neuron-restrictive silencer factor.
abstract: Previous studies have shown that intermittent cold stress (ICS) induces depression-like behaviors in mammals. Tupaia belangeri (the tree shrew) is the only experimental animal other than the chimpanzee that has been shown to be susceptible to infection by hepatitis B and C viruses. Moreover, full genome sequence analysis has revealed strong homology between host proteins in Tupaia and in humans and other primates. Tupaia neuromodulator receptor proteins are also known to have a high degree of homology with their corresponding primate proteins. Based on these similarities, we hypothesized that induction of ICS in Tupaia would provide a useful animal model of stress responses. We exposed young adult Tupaia to ICS and observed decreases in body temperature and body weight in both female and male Tupaia, suggesting that Tupaia are an appropriate animal model for ICS studies. We further examined the efficacy of a new small-molecule compound, C737, against the effects of ICS. C737 mimics the helical structure of neuron-restrictive silencer factor (NRSF/REST), which regulates a wide range of target genes involved in neuronal function and pain modulation. Treatment with C737 significantly reduced stress-induced weight loss in female Tupaia; these effects were stronger than those elicited by the antidepressant agomelatine. These results suggest that Tupaia represents a useful non-rodent ICS model. Our data also provide new insights into the function of NRSF/REST in stress-induced depression and other disorders with epigenetic influences or those with high prevalence in women.
authors.affiliation: Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima-city, Kagoshima 890-0065, Japan.
authors.forename: Chi
authors.initials: C
authors.lastname: Hai-Ying
authors.forename: Kiori
authors.initials: K
authors.lastname: Nagano
authors.forename: Sayeh
authors.initials: S
authors.lastname: Ezzikouri
authors.forename: Chiho
authors.initials: C
authors.lastname: Yamaguchi
authors.forename: Mohammad Enamul Hoque
authors.initials: ME
authors.lastname: Kayesh
authors.forename: Khadija
authors.initials: K
authors.lastname: Rebbani
authors.forename: Bouchra
authors.initials: B
authors.lastname: Kitab
authors.forename: Hirohumi
authors.initials: H
authors.lastname: Nakano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kouji
authors.forename: Michinori
authors.initials: M
authors.lastname: Kohara
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsukiyama-Kohara
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D058639:Cold-Shock Response / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D003863:Depression / Q000209:etiology / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D023421:Models, Animal; D009474:Neurons / Q000502:physiology; D010146:Pain / Q000209:etiology / Q000235:genetics; D012097:Repressor Proteins / Q000502:physiology*; D014417:Tupaia; D015431:Weight Loss / Q000235:genetics; D000099229:RE1-Silencing Transcription Factor; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C084711:agomelatine; D009281:Naphthalenes