Anxiety‐like behavior in female mice changes by feeding, possible effect of guanylate cyclase C

Abstract

Anxiety disorders are the most frequent mental disorders and are more prevalent in the female population. Up to date, an involvement of guanylate cyclase A and B in anxiety‐like behavior has been suggested. In this study, we showed an expression of guanylate cyclase C (GC‐C) in the amygdala which is regulated by feeding. Therefore, we further investigated sex differences of GC‐C effects on anxiety levels with special attention to female estrous cycle and feeding. The effects of estrous cycle and feeding were investigated by several behavior tests: elevated plus maze, home cage escape and novelty‐induced hypophagy. Possible changes in GC‐C expression in amygdala and hypothalamus during estrous cycle were established by qPCR. When GC‐C is activated (after a meal), the sex difference in all behavior tests used was abolished. As the expression of mRNA for GC‐C in the amygdala increases 2 hr after a meal only in female animals, the anxiety levels change after a meal again only in female animals. When the anxiety levels are investigated, it is very important to pay attention not only to estrous cycle in female animals but also when animals were fed compared to the time point of the experiments. Concluding from our results, the sex differences in the incidence of anxiety disorders in humans could be GC‐C dependent.

The use of infrared technology as a novel approach for studies with female laboratory animals

“…For example, authors determined the expression of estrogen receptors in the brainstem ( 22 ) without separating the female rats by estrous phase, although receptors expression changes during the estrous cycle ( 23 ). Our previous study also showed a difference in expression regulation of guanylate cyclase C in the amygdala and hypothalamus during the estrous cycle ( 2 ). Results such as these emphasize the importance of determining the phase of the estrous cycle in any study involving female animals.…”

“…Performing experiments just to meet a requirement yields misleading conclusions and scientifically meaningless results. It is especially important that female animals are in the same phase of their estrous cycles because of a different effect of estrogen and progesterone on numerous physiological and pathological conditions ( 2 , 4 ).…”

“…This problem might be solved by determining the phase of the estrous cycle. Our recent study explained in detail how to correctly perform some behavior tests, and how the estrous cycle affects the collected data and expression of relevant proteins in the amygdala ( 2 ). The effects of estrogens and progesterone on cellular, organ, and body function are numerous, not to mention possible effects on pathological conditions and therapy during different phases of the estrous cycle.…”

Guanylin Peptides Signaling: Insights into Guanylate Cyclase C Dependent and Independent Signaling Pathways

“…Recently, research of effects of UGN/GC-C signaling pathway in the brain and their role in metabolism became a hot topic. GC-C was shown in the rodent brain in neurons of the cerebral cortex, amygdala, midbrain, hypothalamus and Purkinje cells and neurons of deep nuclei of the cerebellum, but also confirmed in the human hypothalamus and prefrontal cortex [33][34][35][36][37][38][39].…”

Sex matters in neuroscience and neuropsychopharmacology

“…Wright et al discuss the need for an integrated translational approach in understanding the neuroscience of social vigilance and social anxiety in adolescent males and females in order to develop effective strategies for treatments (Wright et al, 2019). In keeping with the importance of translational research, Dugandzic et al use a rodent model in their article to show that guanylate cyclase C activation in the amygdala, which is enhanced with feeding (2h after a meal) only in females, is important in the regulation of anxiety-like behaviors and may be an important factor in understanding sex difference in the incidence of anxiety disorders in humans (Dugandzic et al, 2019). Moreover, Fontana et al, report that female zebrafish have higher anxiety-like behavior than males, making zebrafish a valuable model for further understanding the neuroscience of sex differences in anxiety and related disorders (Fontana et al, 2019).…”