Characterization of galanin in the murine brain
The neuropeptide galanin has been implicated in a many central nervous system functions. These range from fundamental processes, such the ability to successfully breed and regulate metabolism, to higher order functions such as the need to learn and remember tactics for finding food, avoiding predators, and choosing mates. To learn more about the role of galanin in the brain, I examined the effects of permanently altered levels of galanin in genetically altered mice. My hypothesis was that enduring changes in galanin levels in mutant animals would produce phenotypes that in turn could provide clues about the roles galanin has in the brain. First, I examined the distribution of galanin gene expression in the brain of the mouse. I found that galanin in widely expressed throughout the brain, in a pattern unique to mice. Second, I sought to determine the role of galanin by using transgenic mice (GALTG), in whom the galanin gene is overexpressed. I found that while GALTG mice had normal neuroendocrine phenotypes, they had significant alterations in levels of galanin receptor mRNA in the hypothalamus, and altered neuropeptide Y (NPY) mRNA in the nucleus accumbens (Acb). I infer from this that compensatory mechanisms act in GALTG mice to keep galanin levels within the physiological range in the hypothalamus, and may serve to counteract the overabundance of galanin in the Acb. Third, I studied the effects of targeted ablation of the galanin gene in knockout mice (GKO). I found that GKO mice had some neuroendocrine abnormalities, but had no changes in galanin receptors or NPY mRNAs in the hypothalamus. This suggests that developmental compensation by galanin receptors or other neuropeptides may not be a generalized strategy in the complete absence of galanin. Fourth, I tried to determine whether NPY and galanin have overlapping roles in the brain by producing and performing an initial characterization of mice with both the galanin and NPY genes ablated (DKO). I discovered that the loss of both galanin and NPY led to phenotypes more severe than seen with single knockouts of these molecules, suggesting that functional overlaps exist between these two widely expressed neuropeptides.