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Publication : Mice lacking proSAAS display alterations in emotion, consummatory behavior and circadian entrainment.

First Author  Aryal DK Year  2022
Journal  Genes Brain Behav Volume  21
Issue  7 Pages  e12827
PubMed ID  35878875 Mgi Jnum  J:335474
Mgi Id  MGI:7443258 Doi  10.1111/gbb.12827
Citation  Aryal DK, et al. (2022) Mice lacking proSAAS display alterations in emotion, consummatory behavior and circadian entrainment. Genes Brain Behav 21(7):e12827
abstractText  ProSAAS is a neuroendocrine protein that is cleaved by neuropeptide-processing enzymes into more than a dozen products including the bigLEN and PEN peptides, which bind and activate the receptors GPR171 and GPR83, respectively. Previous studies have suggested that proSAAS-derived peptides are involved in physiological functions that include body weight regulation, circadian rhythms and anxiety-like behavior. In the present study, we find that proSAAS knockout mice display robust anxiety-like behaviors in the open field, light-dark emergence and elevated zero maze tests. These mutant mice also show a reduction in cued fear and an impairment in fear-potentiated startle, indicating an important role for proSAAS-derived peptides in emotional behaviors. ProSAAS knockout mice exhibit reduced water consumption and urine production relative to wild-type controls. No differences in food consumption and overall energy expenditure were observed between the genotypes. However, the respiratory exchange ratio was elevated in the mutants during the light portion of the light-dark cycle, indicating decreased fat metabolism during this period. While proSAAS knockout mice show normal circadian patterns of activity, even upon long-term exposure to constant darkness, they were unable to shift their circadian clock upon exposure to a light pulse. Taken together, these results show that proSAAS-derived peptides modulate a wide range of behaviors including emotion, metabolism and the regulation of the circadian clock.
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