Fos-Tau-LacZ mice reveal sex differences in brainstem c-fos activation in response to mild carbon dioxide exposure.

There are sex differences in the neurochemistry of brainstem nuclei that participate in the control of breathing as well as sex differences in respiratory responses to hypoxia. Central chemoreception refers to the detection within the brain of minute changes in carbon dioxide (CO(2)) levels and the subsequent modulation of breathing. Putative central chemoreceptor sites are widespread and include cells located near the ventral surface of the brainstem in the retrotrapezoid nucleus (RTN), in the medullary midline raphe nuclei, and, more dorsally in the medulla, in the nucleus of the solitary tract and in the locus caeruleus at the pontomedullary junction as well as in the fastigial nucleus of the cerebellum. In this study, we ask if the cells that respond to CO(2) differ between the sexes. We used a transgenic mouse with a c-fos promoter driven tau-lacZ reporter construct (FTL) to map the locations of cells in the mouse brainstem and cerebellum that responded to exposure of mice of both sexes to 5% CO(2) or room air (control). X-gal (5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside) histochemical staining to detect the beta-galactosidase enzyme produced staining in the brains of mice of both sexes in all of the previously identified putative chemoreceptor sites, with the exception of the fastigial nucleus. Notably, the male RTN region contained significantly more x-gal-labeled cells than the female RTN region. In addition to new observations regarding potential sex differences in the retrotrapezoid region, we found the FTL mouse to be a useful tool for identifying cells that respond to the exposure of the whole animal to relatively low concentrations of CO(2).