Characterizing the architecture and influence of Colony Stimulating Factor-1 and its receptor-bearing cells in the brain
MetadataShow full item record
Colony Stimulating Factor-1 (CSF-1), the primary growth factor for the mononuclear phagocyte lineage, has been shown to play roles in multiple biological functions including immune system activity, development, recovery from injuries, and reproduction. In many of these functions, the underlying mechanism of action is not well understood. The objective of this research was to characterize the role CSF-1 plays in the development of the brain, and in particular, the hypothalamus.;Indeed, numerous lines of evidence support a significant role for CSF-1 in brain function. Using a CSF-1-deficient mouse model, studies from our laboratory have demonstrated that CSF-1 is essential for both male and female reproductive competence, and the lack of CSF-1 during postnatal development results in a number of neurological deficits, perhaps most notably, hypothalamic malfunction. Results from these initial studies raised the intriguing possibility that CSF-1 might be an essential component in the proper development of the brain, and in particular, the hypothalamus.;The goal of this program of research was, therefore, to characterize the spatial and temporal expression patterns of both CSF-1 and its receptor, CSF-1R, as well as to identify the specific cell types in the brain responsible for expressing these potentially critically important proteins. In addition, we assessed the consequences of the lack of CSF-1 signaling on morphological development.;Findings demonstrated that CSF-1R is expressed in the brain during early postnatal development, persists into adulthood, and is present throughout the entire brain. Additionally, results indicated that that CSF-1R is expressed in microglial cells, but not in other cells such as astrocytes, oligodendrocytes, or neurons. Furthermore, in the absence of CSF-1 signaling, we demonstrated that brain morphology is perturbed, and that microglia are virtually absent, particularly in regions related to olfaction.;In conjunction with these findings, we demonstrated, using behavioral methodology, that the olfactory system is impaired in the absence of CSF-1 signaling. Finally, we demonstrated that CSF-1-deficient mice produce normal quantities of gonadotropin-releasing hormone, indicating that the hypothalamic defects do not result from a failure to synthesize this peptide. Findings will help model further research aimed at elucidating the biological importance of CSF-1 in brain activity.
- Theses and Dissertations