DNA topoisomerase I in the mouse central nervous system: Age and sex dependence

Topoisomerase I (topo I) is a nuclear enzyme responsible for the topological state of DNA and therefore participates in most DNA transactions, particularly in transcription. Topo I, a ubiquitous enzyme, was identified and characterized in various cell types and tissues; however, the characterization of topo I in the intact central nervous system was not performed. Here we investigated, for the first time, the activity, level, and distribution pattern of topo I in the various selected brain regions in the mouse. In the visual cortex, cerebellum, and striatum the activity of topo I was 3–4‐fold higher compared to that found in the hippocampus and hypothalamus. Immunohistochemical and immunofluorescence analyses revealed specific distribution patterns of topo I protein in neurons of each of the areas examined. The highest topo I levels were observed in inhibitory neurons. In addition to the expected nuclear localization of this protein, some neurons exhibited significant cytoplasmic content as well. The activity and level of topo I is age‐ and gender‐dependent. It increases from birth to maturity and decreases, more significantly in males, with senescence. These results point to a possible importance and involvement of topo I activity and regulation in various brain functions. J. Comp. Neurol. 493:357–369, 2005. © 2005 Wiley‐Liss, Inc.