engleski

Effect of Guanylate Cyclase-C on Anxiety-like Behavior in Female Mice

INTRODUCTION Anxiety-like disorders are the most common mental disorders in the modern world with an incidence two times higher in women than men. Amygdala, the brain region involved in emotional processing and fear conditioning, shows distinctive structural and physiological sex differences. AIM Since agonists of membrane-bound guanylate cyclase (GC) A and B have been shown to possess anxiolytic properties, the aim of this study is to determine if activation of guanylate cyclase C (GC-C) in amygdala affects anxiety-like behaviour differently in female than in male mice. MATERIALS AND METHODS In this study we used immunohistochemical staining in male and female wild-type (WT) animals, with GC-C knock-out animals (GC-C KO) as controls. GC-C mRNA levels in amygdala and hypothalamus were evaluated using qPCR. Anxiety levels were tested with two behavioural tests (home cage escape, elevated plus maze). Phases of the oestrus cycle were determined by staining vaginal swabs with 0.1% cresyl violet stain and analysis using a stereomicroscope. RESULTS GC-C is expressed in the neurons of basolateral amygdaloid nucleus and the cortical amygdaloidal area. During the oestrous cycle, GC-C expression changes differently in amygdala compared to hypothalamus. Therefore, only female mice in diestrus showed different anxiety levels compared to male mice, which is even more pronounced in GC- C KO mice. As expected, no difference in anxiety levels between genotype was present in male animals. CONCLUSION Female mice demonstrate different anxiety levels during the diestrus phase compared to male animals. GC-C is present in amygdala, and its inhibition during diestrus could be responsible for the difference in anxiety levels between genders and during different phases of the estrous cycle. Our results indicate that GC-C activation may have anxiolytic properties similar to activation of other membrane-bound GCs. ACKNOWLEDGEMENTS This work has been fully supported by Croatian Science Foundation under the project FURNACE (IP- 2018-01-7416).

amygdala, home cage escape, elevated plus maze, estrous cycle

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