Gonadal steroid hormones play an important role in central nervous system development, including brain areas associated with cognition. High levels of progestin binding and progestin receptor (PR) mRNA have been reported in developing cortex, at around the time when the cortex synthesizes high levels of progesterone de novo. Peak levels of PR expression are concurrent with many major growth processes, such as peak dendritic spine and afferent synapse formation in cortical neurons. We used the cellular-level resolution of immunohistochemistry to characterize changes in PR expression within specific cortical lamina over the course of development. The results indicate that PR immunoreactivity (PR-ir) is transiently expressed in specific lamina of frontal, parietal, temporal and occipital cortex. Beginning on E18, PR-ir was observed in subplate cells and then in increasingly superficial lamina (primarily lamina V, then II/III) as postnatal development continued through P13. By P27, this pattern of PR-ir was absent. Double labeling with specific antibodies indicated that PR-ir colocalized with microtubule associated protein (MAP)-2, a neuronal marker, but not with the glial marker, nestin, nor with GABA-ir, suggesting that PR is primarily expressed in excitatory neurons. We also examined whether PR function alters dendritic branching and spine formation on developing cortical cells. Rat pups were subcutaneously injected with the PR antagonist RU486 or oil daily and then sacrificed on P6, P11 or P14. Immunohistochemistry and Western immunoblots were used to measure the levels of synaptic (synaptophysin, syntaxin, spinophilin) and dendritic protein (MAP-2). No differences were found between RU486 and vehicle treated pups in any brain areas examined. These results suggest that specific subpopulations of cortical neurons may be transiently sensitive to progesterone, and that progesterone and its receptor may play a critical role in the fundamental mechanisms underlying normal cortical perinatal development. However, PR influence on perinatal development may exclude effects on cortical synaptogenesis and dendrite formation.
| Identifer | oai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:dissertations-4864 |
| Date | 01 January 2007 |
| Creators | Lopez, Veronica |
| Publisher | ScholarWorks@UMass Amherst |
| Source Sets | University of Massachusetts, Amherst |
| Language | English |
| Detected Language | English |
| Type | text |
| Source | Doctoral Dissertations Available from Proquest |
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