imprint:
Springer Science and Business Media LLC, 2023
Published in:Biology of Sex Differences
Language:
English
DOI:
10.1186/s13293-023-00541-8
ISSN:
2042-6410
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>Aromatase catalyzes the synthesis of estrogens from androgens. Knowledge on its regional expression in the brain is of relevance to the behavioral implications of these hormones that might be linked to sex differences in mental health. The present study investigated the distribution of cells expressing the aromatase coding gene (<jats:italic>Cyp19a1)</jats:italic> in limbic regions of young adult rats of both sexes, and characterized the cell types expressing this gene.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p><jats:italic>Cyp19a1</jats:italic> mRNA was mapped using fluorescent in situ hybridization (FISH). Co-expression with specific cell markers was assessed with double FISH; glutamatergic, gamma-aminobutyric acid (GABA)-ergic, glial, monoaminergic, as well as interneuron markers were tested. Automated quantification of the cells expressing the different genes was performed using CellProfiler. Sex differences in the number of cells expressing <jats:italic>Cyp19a1</jats:italic> was tested non-parametrically, with the effect size indicated by the rank-biserial correlation. FDR correction for multiple testing was applied.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>In the male brain, the highest percentage of <jats:italic>Cyp19a1</jats:italic><jats:sup>+</jats:sup> cells was found in the medial amygdaloid nucleus and the bed nucleus of stria terminalis, followed by the medial preoptic area, the CA2/3 fields of the hippocampus, the cortical amygdaloid nucleus and the amygdalo-hippocampal area. A lower percentage was detected in the caudate putamen, the nucleus accumbens, and the ventromedial hypothalamus. In females, the distribution of <jats:italic>Cyp19a1</jats:italic><jats:sup>+</jats:sup> cells was similar but at a lower percentage. In most regions, the majority of <jats:italic>Cyp19a1</jats:italic><jats:sup>+</jats:sup> cells were GABAergic, except for in the cortical-like regions of the amygdala where most were glutamatergic. A smaller fraction of cells co-expressed <jats:italic>Slc1a3</jats:italic>, suggesting expression of <jats:italic>Cyp19a1</jats:italic> in astrocytes; monoaminergic markers were not co-expressed. Moreover, sex differences were detected regarding the identity of <jats:italic>Cyp19a1</jats:italic><jats:sup>+</jats:sup> cells.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Females show overall a lower number of cells expressing <jats:italic>Cyp19a1</jats:italic> in the limbic brain. In both sexes, aromatase is expressed in a region-specific manner in GABAergic and glutamatergic neurons. These findings call for investigations of the relevance of sex-specific and region-dependent expression of <jats:italic>Cyp19a1</jats:italic> in the limbic brain to sex differences in behavior and mental health.</jats:p>
</jats:sec>