engleski

Guanylate cyclase-C and anxiety-like behavior: gender and estrus cycle differences

Anxiety-like disorders are the most common mental disorders in the modern world with an incidence two times higher in women than in men. Amygdala, the brain region involved in emotional processing and fear conditioning, shows distinctive structural and physiological sexual dimorphism. Agonists of membrane-bound guanylate cyclase (GC) A and B have been shown to possess dose-dependent anxiolytic properties. Therefore, the aim of this study is to determine if activation of guanylate cyclase C (GC-C) in amygdala could affect anxiety- like behaviour differently in female than in male mice. 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). Vaginal swabs were stained with 0.1% cresyl violet stain and analysed using a stereomicroscope to determine the phase of the oestrus cycle. GC-C is expressed in the neurons of basolateral nucleus and cortical area of amygdala. 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. 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 oestrous cycle. Our results indicate that GC-C activation may have anxiolytic properties similar to activation of other membrane-bound GCs. FUNDING: This work has been supported by Croatian Science Foundation under the project FURNACE (IP- 2018-01-7416) and co-financed by the European Union through the European Regional Development Fund, Operational Programme Competitiveness and Cohesion, grant Agreement No. KK.01.1.1.01.0007, CoRE - Neuro.

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

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