title: Lack of estrogen receptor α in astrocytes of progranulin-deficient mice.
abstract: Progranulin (PGRN) is a multifunctional growth factor with functions in neuroprotection, anti-inflammation, and neural progenitor cell proliferation. These functions largely overlap with the actions of estrogen in the brain. Indeed, we have previously shown that PGRN mediates the functions of estrogen, such as masculinizing the rodent brain and promoting adult neurogenesis. To evaluate the underlying mechanism of PGRN in mediating the actions of estrogen, the localization of estrogen receptor α (ERα) in the brains of wild-type (WT) and PGRN-deficient (KO) mice was investigated. First, double-labeling immunofluorescence was performed for ERα with neuronal nuclei (NeuN), ionized calcium-binding adaptor molecule 1 (Iba1), and glial fibrillary acidic protein (GFAP), as markers for neurons, microglia, and astrocytes, respectively, in female mice in diestrous and estrous stages. ERα-immunoreactive (IR) cells were widespread and co-localized with NeuN in brain sections analyzed (bregma -1.06 to -3.16 mm) of both WT and KO mice. In contrast, expression of ERα was not observed in Iba1-IR cells from both genotypes. Interestingly, although ERα was co-localized with GFAP in WT mice, virtually no ERα expression was discernible in GFAP-IR cells in KO mice. Next, the brains of ovariectomized adult female, adult male, and immature female mice were subjected to immunostaining for ERα and GFAP. Again, co-localization of ERα with GFAP was observed in WT mice, whereas this co-localization was not detected in KO mice. These results suggest that PGRN plays a crucial role in the expression of ERα in astrocytes regardless of the estrous cycle stage, sex, and maturity.
authors.affiliation: Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Doke
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuwaki
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yamanouchi
authors.forename: Masugi
authors.initials: M
authors.lastname: Nishihara
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000077155:Granulins; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010052:Ovariectomy; D000077153:Progranulins
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D047628:Estrogen Receptor alpha; D005904:Glial Fibrillary Acidic Protein; D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D000077153:Progranulins