Microglia are reported to have significant roles in regulating normal mammalian adult neurogenesis. There are two neurogenic niches in the adult mammal brain: the subgranular zone (SGZ) in the hippocampus, and the subventricular zone (SVZ), which makes up the lining of the lateral ventricles. While the microglia interactions on adult neurogenesis in the hippocampus have been characterized, the SVZ niche is not as well investigated. The SVZ niche is unique in that the newborn neurons migrate a much longer distance through multiple brain structures compared to newborn neurons in the hippocampus, making it more difficult to fully characterize how microglia influence this process. To examine the SVZ niche and migration pathway, we used the colony stimulating factor 1 receptor (CSF1R) antagonist PLX5622, which promotes brain wide microglia ablation. Microglia ablation resulted in no changes in the numbers of neural stem cells (NSCs), transient amplifying cells, and neuroblasts. Microglia ablation in the olfactory bulb (OB) was decreased compared to the SVZ. CSF1R inhibition had no effect on the ability of microglia to proliferate. Thus, our data suggest that microglia are not required for normal functioning SVZ adult neurogenesis.
Pregnane X Receptor (PXR) is involved in human cancer, either by directly affecting carcinogenesis or by inducing drug-drug interactions and chemotherapy resistance. The clinical significance of PXR expression in invasive breast carcinoma was evaluated in the present study. PXR protein expression was assessed immunohistochemically on formalin fixed paraffin-embedded breast invasive carcinoma tissue sections, obtained from 148 patients, and was correlated with clinicopathological parameters, molecular phenotypes, tumor cells’ proliferative capacity, and overall disease-free patients’ survival. Additionally, the expression of PXR was examined on human breast carcinoma cell lines of different histological grade, hormonal status, and metastatic potential. PXR positivity was noted in 79 (53.4%) and high PXR expression in 48 (32.4%), out of 148 breast carcinoma cases. High PXR expression was positively associated with nuclear grade (p = 0.0112) and histological grade of differentiation (p = 0.0305), as well as with tumor cells’ proliferative capacity (p = 0.0051), and negatively with luminal A subtype (p = 0.0295). Associations between high PXR expression, estrogen, and progesterone receptor negative status were also recorded (p = 0.0314 and p = 0.0208, respectively). High PXR expression was associated with shorter overall patients’ survival times (log-rank test, p = 0.0009). In multivariate analysis, high PXR expression was identified as an independent prognostic factor of overall patients’ survival (Cox-regression analysis, p = 0.0082). PXR expression alterations were also noted in breast cancer cell lines of different hormonal status. The present data supported evidence that PXR was related to a more aggressive invasive breast carcinoma phenotype, being a strong and independent poor prognosticator.
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