Establishment of an intermittent cold stress model using <i>Tupaia belangeri</i> and evaluation of compound C737 targeting neuron-restrictive silencer factor
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Previous studies have shown that intermittent cold stress (ICS) induces depression-like behaviors in mammals. <i>Tupaia belangeri</i> (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 <i>Tupaia</i> and in humans and other primates. <i>Tupaia</i> 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 <i>Tupaia</i> would provide a useful animal model of stress responses. We exposed young adult <i>Tupaia</i> to ICS and observed decreases in body temperature and body weight in both female and male <i>Tupaia</i>, suggesting that <i>Tupaia</i> 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 <i>Tupaia</i>; these effects were stronger than those elicited by the antidepressant agomelatine. These results suggest that <i>Tupaia</i> 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.
- Experimental Animals
Experimental Animals 65(3), 285-292, 2016
Japanese Association for Laboratory Animal Science